Adrenalectomized and nonadrenalectomized Sprague-Dawley rats were addicted to alcohol using a liquid diet supplemented with ethanol by intubation. The rats were sacrificed at various times after ethanol treatment and blood, spleen, and thymus were examined for numbers of lymphocytes and the ability of the lymphocytes to respond to nonspecific T-cell and B-cell mitogens (cell proliferation stimulators). Animals treated with ethanol by inhalation were also tested. Lewis and Sprague-Dawley rats were immunized with sheep red blood cells (SRBC) or TNP-ficol before ethanol treatment, and their ability to respond to an immunization by producing antibodies to the SRBC or TNP-ficol during the period of ethanol administration was tested. Bone marrow cells were also examined to determine the effects of ethanol on the erythroid (red) and myeloid (white) cell progenitors. Both Lewis and Sprague-Dawley rats showed an impaired ability to react to SRBC immunization but not TNP-ficol immunization while being treated with ethanol. Serum corticosterone levels were determined in adrenalectomized as well as normal animals. Animals treated with ethanol showed a decrease in lymphocyte cell numbers in the peripheral blood, spleen, and thymus and an impaired ability of the lymphocytes to respond to nonspecific T-cell and B-cell mitogens. Animals treated with ethanol by inhalation showed a decrease in cell numbers but retained the ability to respond to nonspecific mitogens. Corticosterone levels were increased in ethanol-treated animals. Two corticosterone peaks were seen--one after 2 days of ethanol administration and the other on the day of withdrawal. Seven days after the end of ethanol treatment the rat lymphocytes approached control levels in cell numbers and function. Ethanol treatment, whether by intubation or inhalation, caused a decrease in marrow cellularity and a preferential decrease in colony growth in the erythroid cell line. Further investigations of possible contributing mechanisms of alcohol-induced changes in the immune system are in progress.