Skeletal development on gestation day 21 was examined in fetuses of alcohol-consuming (A), pair-fed (PF) and ad lib-fed (C) Sprague-Dawley females. Ethanol (36% ethanol-derived calories) was administered in liquid diets that were marginal (Diet A1) or optimal (Diet A2) in terms of pregnancy requirements (18% vs. 25% total calories as protein, respectively). For each bone studied, a lengthwise measurement was made of the whole bone and of the ossified portion(s), and percent ossification was calculated. Number of sternebral ossification centers present was also determined. Alcohol-exposed fetuses showed retarded ossification of the tibia and radius, regardless of maternal protein intake. Increasing the protein content of the alcohol diet from 18% (Diet A1) to 25% (Diet A2) significantly increased ossification of the ulna, sternum, humerus and ilium-ischium. For the ulna, A2 fetuses showed greater ossification than A1 fetuses but were still retarded compared to PF and C fetuses. For the sternum, humerus and ilium-ischium, however, ossification in A2 fetuses increased to the levels observed in the PF and C groups. In addition, number of sternebral ossification centers present was significantly increased in A2 compared to A1 fetuses. These data indicate that skeletal development provides a sensitive index of ethanol-induced developmental delay as well as interactive effects of ethanol and nutrition. © 1990.