Ten chemotherapeutic agents, mostly phase I and II drugs, were tested for activity against two human lymphomas heterotransplanted in nude mice. Three of these agents have been tested in phase II trials in patients with lymphoma and found to lack activity; a corresponding lack of activity was found in lymphoma-bearing nude mice. Apart from cyclophosphamide, which is known to have activity against lymphoma and was used as a positive control, only dianhydrogalactitol (DAG) had antitumor activity in the lymphoma-bearing nude mice. Tumor regressions induced by DAG in a heterotransplanted diffuse histiocytic lymphoma were determined to be significant using a statistical method designed for such studies. These data suggest there should be further study of DAG in patients with lymphoma.