The present study was undertaken to assess the possible interactive effects of prenatal ethanol exposure and stress in adulthood on lymphocyte populations in rat offspring, and to examine differential vulnerability of males and females to these challenges. Male and female offspring from prenatal ethanol-exposed (E), pair-fed, and ad libitum-fed control conditions were exposed to a 3-week chronic intermittent stress regimen in adulthood. Animals were exposed to two of six different stressors daily, one each at random times in the morning and afternoon, with the same pair of stressors being repeated every 4 days. Following the 3-week stress period, lymphocytes from four compartments (peripheral blood, spleen, thymus, and cervical lymph nodes) were analyzed for expression of differentiation antigens. Data demonstrate that, whereas a number of the effects of prenatal ethanol on lymphocyte populations appeared to be nutritionally mediated, the additional challenge of exposure to stressors differentially affected animals exposed to ethanol prenatally and appeared to have effects primarily in male offspring. Stressed E males had a greater reduction in the number of pan T-cells in the thymus and peripheral blood, compared with nonstressed E males, but showed an increased peripheral blood pan T-antigen expression. Stressed E males also had reduced numbers of peripheral blood CD4+ T cells compared to nonstressed E males [corrected].(ABSTRACT TRUNCATED AT 250 WORDS)