The effect of morphine on tumor growth of EL-4 leukemia in C57BL/6 mice and of Sarcoma 180 carcinoma in ddY mice was studied. Local subcutaneous tumor growth was enhanced by morphine (10 mg/kg, s.c.) given daily for 10d. This effect was inhibited by preadministration of the opioid antagonist naloxone. However, naloxone alone had no significant effect on tumor growth. Morphine also enhanced tumor growth in C57BL/6 mice inoculated i.p. with P388 as well as Meth-A cell in Balb/c mice. However, incubation of morphine with cultures of EL-4, P388, MM-46 and Meth-A cells failed to enhance tumor growth. Mice given morphine displayed marked atrophy and reduced cellularity of the spleen and thymus. The humoral response to sheep erythrocytes and T- and B-cell responses to foreign antigens were suppressed, and the lymphocyte proliferative response to T- and B-cell mitogens (concanavalin A and bacterial lipopolysaccharide, respectively) was attenuated. Morphine exerted an inhibitory effect on the immune response which was antagonized by the concomitant administration of naloxone. These data suggest that the enhancement of tumor growth by the administration of morphine is the result of a overall immunosuppressive effect. The significance of the immunomodulatory effect of morphine is discussed in this report.