The article discusses strategies for multilocus linkage analysis in humans, focusing on the detection of linkage and estimation of recombination. The authors investigate the relative efficiency of two-point and three-point linkage tests for detecting linkage and estimating recombination in various situations. They developed the computer program LINKAGE for multilocus linkage analysis. The study proposes a method for location scores to efficiently detect linkage between a disease locus or new genetic marker and a previously established linkage group. This method is illustrated using simulated pedigree data similar to Duchenne muscular dystrophy. The results show that appropriate strategies can significantly improve the efficiency and accuracy of genetic mapping. Various methods are available for investigating relationships between genetic loci in humans. Somatic cell hybrids provide physical assignments of loci on human chromosomes, while family-based linkage analysis constructs genetic maps. The latter approach allows the detection of linkage and estimation of recombination rates, which are important for understanding genetic parameters. The new wealth of DNA polymorphisms will lead to the development of new strategies for family-based linkage analysis. When only about 30 genetic markers were available, a natural approach for detecting linkage between a disease locus and markers was pairwise analysis. The classical method of lod-scores was originally restricted to simple Mendelian traits and nuclear families but was later extended to complex phenotypes and general pedigrees. More than 200 DNA polymorphisms have been defined in recent years, and it is expected that the number required to span the human genome will soon be reached. This raises questions about the relative merits of two-point and multipoint linkage analysis. Although multipoint tests are generally more efficient than pairwise tests, a systematic investigation is needed before new approaches can be proposed. The determination of a genetic map from linkage analyses requires assumptions about the mathematical relationships between map distance and recombination frequency. Various mapping functions have been proposed, some of which assume specific assumptions regarding interference. The authors examine the relative efficiency of two-point and three-point linkage tests under various conditions. They consider the relevance of multilocus analysis for constructing genetic maps and propose a strategy for detecting linkage and adding a new locus to a known genetic map. The computer program package LINKAGE has been developed for this investigation. The study also discusses the advantages of multilocus analysis, including the ability to account for the nonindependence of recombination estimates and the increased precision of estimated locations on the genetic map. The authors propose a method of location scores with some analogy to the classical lod-score curve, which allows an easy combination of results from different studies. The example illustrates the method of location scores using simulated data for a situation akin to Duchenne muscular dystrophy. The results show that multilocus analysis can substantially improve the efficiency and accuracy of linkage analysis and genetic mapping.The article discusses strategies for multilocus linkage analysis in humans, focusing on the detection of linkage and estimation of recombination. The authors investigate the relative efficiency of two-point and three-point linkage tests for detecting linkage and estimating recombination in various situations. They developed the computer program LINKAGE for multilocus linkage analysis. The study proposes a method for location scores to efficiently detect linkage between a disease locus or new genetic marker and a previously established linkage group. This method is illustrated using simulated pedigree data similar to Duchenne muscular dystrophy. The results show that appropriate strategies can significantly improve the efficiency and accuracy of genetic mapping. Various methods are available for investigating relationships between genetic loci in humans. Somatic cell hybrids provide physical assignments of loci on human chromosomes, while family-based linkage analysis constructs genetic maps. The latter approach allows the detection of linkage and estimation of recombination rates, which are important for understanding genetic parameters. The new wealth of DNA polymorphisms will lead to the development of new strategies for family-based linkage analysis. When only about 30 genetic markers were available, a natural approach for detecting linkage between a disease locus and markers was pairwise analysis. The classical method of lod-scores was originally restricted to simple Mendelian traits and nuclear families but was later extended to complex phenotypes and general pedigrees. More than 200 DNA polymorphisms have been defined in recent years, and it is expected that the number required to span the human genome will soon be reached. This raises questions about the relative merits of two-point and multipoint linkage analysis. Although multipoint tests are generally more efficient than pairwise tests, a systematic investigation is needed before new approaches can be proposed. The determination of a genetic map from linkage analyses requires assumptions about the mathematical relationships between map distance and recombination frequency. Various mapping functions have been proposed, some of which assume specific assumptions regarding interference. The authors examine the relative efficiency of two-point and three-point linkage tests under various conditions. They consider the relevance of multilocus analysis for constructing genetic maps and propose a strategy for detecting linkage and adding a new locus to a known genetic map. The computer program package LINKAGE has been developed for this investigation. The study also discusses the advantages of multilocus analysis, including the ability to account for the nonindependence of recombination estimates and the increased precision of estimated locations on the genetic map. The authors propose a method of location scores with some analogy to the classical lod-score curve, which allows an easy combination of results from different studies. The example illustrates the method of location scores using simulated data for a situation akin to Duchenne muscular dystrophy. The results show that multilocus analysis can substantially improve the efficiency and accuracy of linkage analysis and genetic mapping.