There are reports that fetal alcohol syndrome (FAS) is associated with immune deficiency or DiGeorge syndrome. To investigate the effect of prenatal alcohol exposure on the immune system, we used a mouse model of FAS in which C57BL/6J female mice were fed a complete liquid diet containing 25% ethanol-derived calories (EDC) from gestational day (g.d.) 1 to 18. Thymus cell numbers were markedly reduced in 18-day fetuses exposed to ethanol. Thymocytes from fetuses from the 25% EDC diet group and from pair-fed and ad-libitum control diet groups were compared by flow cytometry for expression of T cell differentiation antigens. The proportions of L3T4- and Lyt-2 positive thymus cells were significantly reduced in alcohol-exposed fetuses compared to controls; however, the number of Thy-1-positive cells did not differ among any of the groups. Six-day old neonates exposed prenatally to ethanol from g.d. 1 to 13 had thymus and spleen T cell populations similar to those of controls in almost all cases, indicating a "catch-up" of T cell numbers in most animals. Spleen T cell function, assessed by response to Concanavalin A (Con A), or Con A plus T cell growth factors, was somewhat depressed in ethanol-exposed 6-day pups.