We have isolated the Drosophila disc proliferation abnormal (dpa) gene, a member of the MCM family of DNA replication factors. Members of this family of proteins are required for DNA replication in yeast. A dpa null mutant dies during pupal stages because imaginal tissues necessary for the formation of the adult fly fail to proliferate normally. Beginning in late embryogenesis BrdU labeling reveals DNA replication defects in mitotically proliferating cells. In contrast, dpa is dispensable for endoreplication, a specialized cell cycle consisting of consecutive rounds of S phases without intervening mitosis. Our studies suggest an essential role for dpa in mitotic DNA replication but not in endoreplication. Thus, dpa is not a general replication factor but may play a specialized regulatory role in DNA replication.