Mononuclear leukocytes isloated from the blood of previously treated patients with advanced active Hodgkin disease contained high concentrations of monocytes and showed poor lymphocyte blastogenesis to mitogens. In five of eight patients with disseminated disease, blastogenesis became normal or improved markedly when the leukocyte suspensions were depleted of monocytes before culture. Addition of autologous macrophages to the monocyte-depleted lymphocytes resulted in a reappearance of the inhibition of blastogenesis. Monocyte inhibition was associated with the presence of active disease, lymphocytopenia, and low lymphocyte/monocyte ratios in the peripheral blood. The role of previous treatment is uncertain, since inhibition tended to disappear when the patients were retreated. Inhibitory monocyte-lymphocyte interactions may be one of the causes of impaired cell-mediated immunity in Hodgkin disease.