This study was initiated to evaluate the effects of caffeine on the actions of the DNA synthesis inhibitor, 5-fluoro-2-deoxyuridine(FUdR) and the anticancer drug, mitomycin C. FUdR or mitomycin C were injected intraperitoneally to pregnant mice, and caffeine was subcutaneously injected simultaneously. Following conclusions were made from the comparative analyzing the congenital malformations and chromosomal aberrations caused by the drugs used above. 1. The number of viable fetus due to FUdR or mitomycin C was decreased significantly by caffeine. 2. The frequency of external malformations caused by FUdR or mitomycin C treatment increased significantly by caffeine. 3. The occurrence of micronucleus in maternal bone marrow cells and fetal blood cells due to FUdR or mitomycin C treatment increased significantly by caffeine with similar frequency. 4 The mitotic index due to FUdR or mitomycin C was decreased significantly by caffeine treatment, especially in the fetal liver. 5. the frequency of chromosomal aberrations due to FUdR or mitomycin C increased significantly both in the fetal liver and the maternal bone marrow. Therefore, this study suggests that caffeine potentiate the effects of FUdR or mitomycin C for the induction of congenital malformation and chromosomal aberration in the mice.