Previous reports of an association between cigarette smoking and the depression of immune function were investigated by studies of 35 subjects before, and three months after, they had ceased to smoke cigarettes. The studies included tests of natural killer cell (NK) activity against several target cells and the measurement of immunoglobulin levels in sera and saliva. Similar tests were conducted on 29 control subjects who continued to smoke. The results indicated a significant decrease in lymphocyte counts and a significant increase in NK activity against cultured melanoma cells in subjects who ceased smoking. Serum IgG and IgM levels rose significantly in those who ceased smoking cigarettes, but there was no change in IgA levels. Similar increases in immunoglobulin levels (IgA and IgG) in mucosal secretions (saliva) were noted after cessation of smoking. The NK activity and immunoglobulin levels of smokers who continued to smoke did not show significant changes. These results were consistent with the reversal of changes in immune function associated with smoking. We suggest that these findings may provide further insight into the association of smoking with an increased incidence of certain malignant diseases and respiratory infections.