Using the Saccharomyces cerevisiae MATa/MATα ORF deletion collection, homozygous deletion strains were identified that undergo mating with MATa or MATα haploids. Seven homozygous deletions were identified that confer enhanced mating. Three of these, lacking CTF8, CTF18, and DCC1, mate at a low frequency with either MATa or MATα haploids. The products of these genes form a complex involved in sister chromatid cohesion. Each of these strains also exhibits increased chromosome loss rates, and mating likely occurs due to loss of one copy of chromosome III, which bears the MAT locus. Three other homozygous diploid deletion strains, ylr193cΔ/ylr193cΔ, yor305wΔ/yor305wΔ, and ypr170cΔ/ypr170cΔ, mate at very low frequencies with haploids of either or both mating types. However, an ist3Δ/ist3Δ strain mates only with MATa haploids. It is shown that IST3, previously linked to splicing, is required for efficient processing of the MATa1 message, particularly the first intron. As a result, the ist3Δ/ist3Δ strain expresses unbalanced ratios of Matα to Mata proteins and therefore mates with MATa haploids. Accordingly, mating in this diploid can be repressed by introduction of a MATa1 cDNA. In summary, this study underscores and elaborates upon predicted pathways by which mutations restore mating function to yeast diploids and identifies new mutants warranting further study.