Recent comparisons of chromosome replication in meiotic and mitotic cells have revealed significant differences in both the rate and pattern of DNA synthesis during the final duplication preceding meiosis. These differences suggested that unique gene functions might be required for premeiotic replication that were not necessary for replication during growth. To provide evidence for such functions, we isolated stage-specific mutants in the yeast Saccharomyces cerevisiae which permitted vegetative replication but blocked the round of replication before meiosis. The mutants synthesized carbohydrate, protein, and RNA during the expected interval of premeiotic replication, suggesting that their lesions preferentially affected synthesis of DNA. The mutations blocked meiosis, as judged by a coincident inhibition of intragenic recombination and ascospore formation. The lesions were characterized as recessive nuclear genes, and were designated mei-1, mei-2, and mei-3; complementation indicated that the relevant gene products were not identical.