To determine the relative efficacy of mechlorethamine hydrochloride and vinblastine sulfate, 172 patients with Hodgkin's disease, lymphosarcoma, and reticulum cell sarcoma were randomly assigned to receive one or the other of these agents. If treatment with the first compound failed, each patient was to be treated with the second. No significant differences were found between the therapeutic results obtained with these two drugs in any of these illnesses. The Rye classification for Hodgkin's disease was not found to be of prognostic value for response to these agents. The patients with nodular, poorly differentiated lymphocytic lymphoma according to the Gall-Rappaport classification for non-Hodgkin's lymphoma, responded significantly better to mechlorethamine than to vinblastine, and their response rate with the alkylating agent was significantly higher than that of the other persons with non-Hodgkin's lymphoma.