Using a screen designed to identify yeast mutants specifically defective in recombination between homologous chromosomes during meiosis, we have obtained new alleles of the meiosis-specific genes, HOP1, RED1, and MEK1. In addition, the screen identified a novel gene designated MSH5 (MutS Homolog 5). Although Msh5p exhibits strong homology to the MutS family of proteins, it is not involved in DNA mismatch repair. Diploids lacking the MSH5 gene display decreased levels of spore viability, increased levels of meiosis I chromosome nondisjuction, and decreased levels of reciprocal exchange between, but not within, homologs. Gene conversion is not reduced. Msh5 mutants are phenotypically similar to mutants in the meiosis-specific gene MSH4 (Ross-Macdonald and Roeder 1994). Double mutant analysis using msh4 msh5 diploids demonstrates that the two genes are in the same epistasis group and therefore are likely to function in a similar process--namely, the facilitation of interhomolog crossovers during meiosis.