The study was designed to determine what type of potentiation,.if any, occurred between caffeine and acetazolamide. Caffeine (75 mg/kg) and/or acetazolamide (200, 1000, or 1500 mg/kg) were administered to pregnant C57BL/6J dams on day 9 of gestation. Fetuses were removed on the eighteenth day of gestation via cesarean section and examined for gross morphological malformations using a Bausch & Lomb SKV1070P dissecting microscope. Treatment with HD-ACZM and HD+CAFF resulted in a reduction of fetal weight. Maternal exposure to MD-ACZM and HD-ACZM caused a statistically significant (P < .001) and dose-dependent increase in the percent of C57BL/6J fetuses with ectrodactyly along with increased severity of the defects displayed (relative to controls). An increase in the number of ectrodactylous fetuses and the severity of defects was also observed in all groups administered caffeine and acetazolamide, reaching statistical significance in the MD+CAFF and HD+CAFF groups (P < .001). Because potentiation of the teratogenic effects of acetazolamide was exhibited only in the MD+CAFF vs. MD-ACZM groups, the type of potentiation occurring between caffeine and acetazolamide can not be determined.