Mitoxantrone was administered to 74 dogs with lymphoma at a dosage of 5.0 mg/m2 of body surface, IV, every 3 weeks. Thirty-four dogs had failed to respond to prior treatment with chemotherapeutic agents, which included doxorubicin (33 dogs). The remaining 40 dogs had not received prior treatment. Complete remission was determined in 19 of 74 dogs (26%), 10 of which had not received prior treatment. The median duration of remission for these 10 dogs was 94 days (range, 49 to 440 days, with 2 dogs still alive at 370 and 440 days, respectively). Nine dogs that had received prior treatment had complete remission that lasted for a median of 126 days (range, 42 to 792 days, with 1 dog still alive at 792 days). The combined remission rate (complete remission plus partial remission) was 41%. Toxicosis was minimal, developing in only 9 dogs and requiring hospitalization of 2 dogs. We concluded that the complete remission rate ascertained when mitoxantrone was the only treatment administered was low, compared with treatments that involved other chemotherapeutic agents; however, the combined remission rate of 41% indicated that mitoxantrone may be beneficial in the treatment of lymphoma in dogs.