A group of 28 healthy, white, male, light-to-moderate smokers, 21 to 35 years of age, were offered a financial inducement to abstain from smoking for 31 days. A matched control group of 11 smokers were paid to continue smoking during the same period. Nonspecific parameters of immune system function were monitored before and at various times after smoking abstinence. Abstinence increased natural killer cell cytotoxic activity but did not alter mitogen-induced T-lymphocyte proliferation as measured by responses to concanavalin A or phytohemagglutinin. Serum cortisol concentrations also decreased after smoking cessation; however, changes in immune function were not correlated with serum cortisol change, nor with indices of smoking such as plasma nicotine and cotinine levels. Responses to concanavalin A and phytohemagglutinin were positively correlated with change in self-reported alcohol ingestion during smoking abstinence. Results indicate that elevation in natural kill cell cytotoxic activity is detectable within 1 month of smoking cessation, even in light-to-moderate smokers. However, elevation in natural killer cell cytotoxic activity appears not to be directly related to cessation-induced reductions in plasma nicotine, cotinine, or circulating cortisol levels. (J ALLERGY C LIN IMMUNOL 1995;95:901–10.)