Fetal alcohol syndrome is a significant preventable health problem world wide. Studies in humans and animals suggest that prenatal ethanol exposure (E) also disrupts the normal development of the immune system, resulting in immune disfunction that may persist well into adult life. Data also indicate that stress can have a profound negative impact on immunocompetence. The proposed research is the first to investigate the interactive effects of prenatal ethanol and postweaning stress on immunocompetence. We have shown that E results in: 1) long-term effects on offspring immunocompetence; 2) alterations in the hypothalamic-pituitary-adrenal (HPA) response to stress, Our preliminary studies demonstrate interactive effects of prenatal ethanol and stress in adulthood on lymphocyte populations. The proposed research will focus on one critical aspen of the immune response, T cell--B cell interactions. The ability of T helper cells to facilitate immunoglobulin production by B cells, and conversely, the ability of B cells to respond to T lymphocyte-derived activation and proliferation signals, will be assessed. In adulthood, offspring will be subjected to a 3 week chronic intermittent stress regimen or will remain undisturbed. Experiments in which mitogen-activated T cell supernatants from both prenatally treated and control animals are cultured with activated B cells from both prenatally treated and control animals will allow us to determine if the potential defect lies on the T cell or the B cell side of this system, or if both cell types are functioning abnormally. Our working hypothesis is that prenatal ethanol will cause abnormal T cell--B cell interactions, via either defective T cell activation or aberrant lymphokine production by activated T cells. Our experimental paradigm will also enable us to determine whether B cells are affected. We also hypothesize that stress will exacerbate the immunosuppressive effects of prenatal ethanol, and based on our previous data, that males will be more affected than females by exposure to prenatal ethanol and stress. This approach will increase our understanding of two fundamentally important issues: the nature of the immunoteratogenic effects of ethanol, and the possible role of stress in exacerbating these effects.