This study examined the interactive effects of ethanol and nutritional status on pituitary-adrenal function of pregnant females consuming high doses of ethanol throughout gestation. Three liquid diets were formulated ranging in protein content from suboptimal to supraoptimal (18%, 25%, or 32% of total calories) in terms of pregnancy requirements, while ethanol was held constant at high levels (36% of total calories). In addition to the alcohol group (A), both pair-fed (PF) and ad libitum-fed control (C) groups were included in each diet regimen. Basal levels of corticosterone and the adrenocortical response to stress were measured in dams on days 11, 16, or 21 of gestation. Plasma levels of corticosterone-binding globulin (CBG) were also measured on gestation days 16 and 21. Maternal adrenal weights, basal corticosterone levels, the adrenocortical response to stress, and the corticoid stress increment were all significantly increased in A compared to both PF and C females. Plasma CBG levels of A females were similar to or less than those of PF and C females. Thus alcohol consumption significantly increased maternal pituitary-adrenal activity as early as day 11 of gestation and these effects on hormonal function increased as gestation progressed. This adrenocortical hyperactivity was relatively unaffected by maternal nutritional status and thus appears specific to alcohol.