Immunosuppression in 45 patients with lung cancer was studied by examining delayed cutaneous hypersensitivity reactions to DNCB and by analyzing the effect of the patient's serum on the proliferative response of normal donor lymphocytes. Both diminution of DNCB reactivity and inhibition of the proliferative response of normal donor lymphocytes to mitogens were associated with the stage of the disease and the presence of unresected tumor. Suppressive sera were associated with poor prognosis. The suppressive effects of patients' sera on lymphocytes from a normal donor suggest that the immunosuppression seen in lung cancer may be mediated by serum factors. The significant association of clinically evident tumor with this serum-mediated immunosuppression further suggests that the tumor itself could account for the appearance of these factors in the host. The clinical implications of these findings may be useful for designing new clinical trials.