ObjectiveEpidemiological data suggest that the presence of a depressed mood combined with cigarette smoking increases the risk of cancer at sites associated with smoking and at sites not associated with smoking. This study tested the hypothesis that major depression and smoking together contribute to a decline of natural killer cell (NK) activity, an immune parameter thought to be important in immune surveillance.MethodsA sample of 245 men were stratified into four groups: control subjects who were not smokers, control subjects who were smokers, subjects with major depression who were not smokers, and subjects with major depression who were smokers. Blood samples were obtained for measurement of total white blood cell (WBC) counts, differential cell counts, and assay of NK activity.ResultsMajor depression and cigarette smoking interact and were together associated with changes in WBC counts and NK activity. Depressed subjects who were smokers had higher WBC counts (p < .001) and lower NK activity (p < .01) than depressed nonsmoking subjects. However, WBC counts and NK activity were similar in control smokers and nonsmokers. Backward elimination regression analyses showed that the interaction of depression and smoking significantly (p < .001) predicted WBC counts and NK activity.ConclusionsThis study extends previous findings of immune alterations in patients with major depression. Major depression and smoking interact and together contribute to an elevation of total WBC count and a decline of NK activity.