This study presents a comprehensive two-hybrid analysis to explore the protein interactome of *Saccharomyces cerevisiae*. The researchers developed a system to examine all possible two-hybrid interactions between approximately 6,000 proteins in the yeast genome. They identified 4,549 two-hybrid interactions among 3,278 proteins, which significantly expanded the existing knowledge of yeast protein interactions. The cumulative analysis of these binary interactions formed a large network linking most of the proteins, with bioinformatics aiding in the selection of biologically relevant subnetworks. These subnetworks included intriguing findings, such as the involvement of a novel protein in spindle pole body function and the potential identification of an unidentified multiprotein complex involved in vesicular transport. The study highlights the importance of comprehensive protein interaction mapping for functional genomics and provides valuable insights into the cellular machinery. However, the study also demonstrates the limitations of large-scale two-hybrid approaches, emphasizing the need for multiple independent projects and the integration of different methods to improve the reliability and accuracy of the data.This study presents a comprehensive two-hybrid analysis to explore the protein interactome of *Saccharomyces cerevisiae*. The researchers developed a system to examine all possible two-hybrid interactions between approximately 6,000 proteins in the yeast genome. They identified 4,549 two-hybrid interactions among 3,278 proteins, which significantly expanded the existing knowledge of yeast protein interactions. The cumulative analysis of these binary interactions formed a large network linking most of the proteins, with bioinformatics aiding in the selection of biologically relevant subnetworks. These subnetworks included intriguing findings, such as the involvement of a novel protein in spindle pole body function and the potential identification of an unidentified multiprotein complex involved in vesicular transport. The study highlights the importance of comprehensive protein interaction mapping for functional genomics and provides valuable insights into the cellular machinery. However, the study also demonstrates the limitations of large-scale two-hybrid approaches, emphasizing the need for multiple independent projects and the integration of different methods to improve the reliability and accuracy of the data.