Canine lymphoma is a frequently occurring, temporarily controllable form of cancer that is similar to high-grade non-Hodgkins lymphoma in people. The best conventional chemotherapy results in rapid improvement, but ultimately relapse and progression occur. Adjustment of current chemotherapy protocols is unlikely to result in substantial gains in survival due to development of multiple mechanisms of drug resistance occurring during treatment. Therefore, new strategies that have demonstrated efficacy in humans are worth developing for dogs. An antibody that recognizes cancer cells and stimulates the patient’s immune system to eliminate the cancer is an example of such a strategy. We have determined that an antibody made against human lymphocytes cross-reacts with canine lymphoma and causes cell death. This antibody has been confirmed to be safe in normal dogs. We propose to optimize the administration of this antibody in dogs that have already failed chemotherapy for lymphoma. We will evaluate the safety and potential efficacy of this antibody as a prelude to more extensive testing in dogs with lymphoma. This antibody also recognizes cells from dogs with malignant histiocytosis and may be useful for management of this disorder as well.