To examine the dietary interrelationships of glucose and lipid on embryological growth and development, two levels of glucose (0% and 24%) and two types of lipid--soybean oil (SBO; 44.5% 18:2[n-6]) or oleic acid (OL; 6.7% 18:2[n-6])--were fed to pregnant rat dams until Day 12.5 of gestation, when developing embryos and maternal tissues were collected for analysis. In addition, Day 9.5 embryos were obtained from the dietary treatment groups and cultured in vitro until Day 12.5 to ascertain whether or not the embryos showed developmental changes in response to dietary treatment in the absence of maternal and placental factors. Differences in energy intake and macronutrient composition explained differences in early placental weight; macronutrient composition, but not energy intake, accounted for differences in weight of in vivo embryos and in morphological scores of cultured embryos. With food intake as a covariate in the statistical analysis, the results showed that only the level of maternal dietary glucose influenced the number of live embryos and resorptions per litter. Both the level of carbohydrate and the type of lipid in the maternal diet, however, independently and interactively affected both embryonic growth and development in vivo and in culture. To evaluate the biological significance of this dietary interaction, concentrations of essential fatty acids in the embryonic and maternal tissues were measured. A striking result of this study was the rapidity of the diet-induced changes in tissue fatty acid composition. By gestational Day 12.5, the lack of glucose in the OL-based diet was associated with a raised 18:2 (n-6)/20:4 (n-6) ratio and a lowered 20:4 (n-6) content in the embryo and the maternal liver. We suggest that a carbohydrate-free maternal diet with apparently adequate levels of essential fatty acid can contribute to embryonic growth retardation both in vivo and in vitro by perturbing embryonic essential fatty acid metabolism.