This study comprehensively analyzes gene expression differences between sexes in multiple somatic tissues of 334 mice derived from an intercross between C57BL/6J and C3H/HeJ strains. The analysis, based on microarray data from 23,574 transcripts, reveals a much greater extent of sexual dimorphism in gene expression than previously recognized. Thousands of genes show sexual dimorphism in liver, adipose, and muscle, and hundreds in brain. These genes exhibit tissue-specific patterns of expression and are enriched for distinct pathways in the Gene Ontology database. Chromosomal enrichment is observed not only on sex chromosomes but also on several autosomes. Genetic analyses indicate global regulation of subsets of sexually dimorphic genes, with transcript levels controlled by expression quantitative trait loci (eQTL) hotspots that exhibit tissue-specific control. Many tissue-specific transcription factor binding sites are also enriched in these genes. The study provides insights into the mechanisms underlying physiological differences between sexes and their relevance to common diseases.This study comprehensively analyzes gene expression differences between sexes in multiple somatic tissues of 334 mice derived from an intercross between C57BL/6J and C3H/HeJ strains. The analysis, based on microarray data from 23,574 transcripts, reveals a much greater extent of sexual dimorphism in gene expression than previously recognized. Thousands of genes show sexual dimorphism in liver, adipose, and muscle, and hundreds in brain. These genes exhibit tissue-specific patterns of expression and are enriched for distinct pathways in the Gene Ontology database. Chromosomal enrichment is observed not only on sex chromosomes but also on several autosomes. Genetic analyses indicate global regulation of subsets of sexually dimorphic genes, with transcript levels controlled by expression quantitative trait loci (eQTL) hotspots that exhibit tissue-specific control. Many tissue-specific transcription factor binding sites are also enriched in these genes. The study provides insights into the mechanisms underlying physiological differences between sexes and their relevance to common diseases.