A C57BL/6J mouse model was used to examine the coteratology of alcohol and cocaine. Plugged female mice were assigned to one of four treatment groups: control, cocaine only, alcohol only, or alcohol-cocaine. Experimental animals were treated from gestation day (GD) 6-18 and were killed the morning of GD 19. Alcohol was administered in a liquid diet containing 25% ethanol-derived calories (25% EDC), and cocaine was administered daily in subcutaneous injections of 60 mg/kg. All groups were pair-fed to the alcohol-cocaine group. The results showed that the cocaine-only and the alcohol-cocaine group had fewer successful pregnancies. The alcohol-only group had the lowest maternal weight gain from GD 1-19. There were no treatment group effects on litter size, sex ratio, or prenatal mortality. Importantly, fetuses in the alcohol-cocaine group weighed less than all other groups and had the greatest occurrence of fetal anomalies. These data confirm the teratogenic effects of alcohol and cocaine and suggest that the combination of the two drugs, if administered chronically, is more deleterious to pregnancy and fetal outcome than either drug alone. (C) 1999 Elsevier Science Inc. All rights reserved.