Alcohol is a known suppressant to the immune system, and alcoholics frequently have impaired humoral and cell-mediated immunity. Several studies indicate that alcohol modulates natural killer (NK) cell activity. NK cells provide important defense against certain infectious diseases, spontaneously arising tumors and, in particular, to blood-borne metastasizing tumor cells. Evaluation of the effects of alcohol on NK cells is complicated by many factors including: the level and duration of alcohol abuse, polydrug use, the subject's age, and nutritional and health status. This study examined the effects of 1 and 2 weeks of alcohol consumption on baseline and interleukin 2 (IL-2) stimulated murine NK cell activity. Well nourished female C57BL/6 mice were given continuous access to 20% w/v ethanol as the sole fluid source and consumed about 40% of their total caloric intake as ethanol. Splenic baseline and IL-2 stimulated NK cell activity were significantly lower in ethanol-consuming groups compared to control groups after the 1- and 2-week test periods. The average daily intake of ethanol, blood alcohol concentration, and the percentage of ethanol-derived calories were not associated with the decreased NK cell activity of the experimental animals; nor did any other measured parameter appear to serve as an indicator of ethanol modulation of splenic NK cell activity. Whether this immunosuppression results from the "direct" modulation of ethanol or from indirect factors is presently unknown.