A clinical trial of ICRF-159 was done in patients with Hodgkin's disease and non-Hodgkin's lymphomas whose tumors had become resistant to conventional chemotherapy. Antitumor effect and toxicity were compared in patients who were randomly assigned to receive either a loading course or a weekly regimen. Among 82 evaluable cases, five of 39 (13%) treated with the loading course schedule and six of 43 (14%) treated with the weekly schedule experienced objective tumor regressions. Response duration tended to be brief (median, 7 weeks). Life-threatening myelosuppression was more frequent in patients receiving the loading course regimen. Survival was somewhat longer among patients receiving the weekly schedule (median survival, 24 versus 12 weeks; P = 0.04). ICRF-159 demonstrated definite but limited therapeutic activity in this population of patients with advanced malignant lymphomas. The weekly schedule was associated with fewer episodes of life-threatening toxicity and longer patient survival.