Fifty cats with feline leukemia virus (FeLV) infection and leukemia-lymphoma complex were treated by ex vivo immunoadsorption with Staphylococcus protein A-bound filters. Most cats responded to therapy. Twelve showed tumor regression, including disappearance of tumor cells, but died later of other complications. Three have had long-term remission of more than 1 year and remain healthy. A consistent finding in these three cats was the appearance during treatment of a complement-dependent cytotoxic antibody against cat lymphoma cells (FL-74). The cytotoxic antibody increased substantially during treatment. Appearance and increase of the cytotoxic antibody was associated with disappearance of FeLV from blood and remission of leukemia. By electroblot analysis, antibody to FeLV protein (Mr, 70,000) was detected in serum prior to detection of the cytotoxic antibody. The cytotoxic antibody was found by immunofluorescence to be specific for antigens on membranes of viable FL-74 cells. By using monoclonal antibodies to FL-74 cells and to components of FeLV, the cytotoxic antibody was shown to be directed against gp70, a glycoprotein of Mr 70,000, but not against p27 of FeLV or other membrane antigen(s) of FL-74 cells. The development of a high concentration of cytotoxic antibody to FeLV gp7O may play an important role in tumor regression and in disappearance of FeLV infection.Ex vivo immunoadsorption by Staphylococcus protein A (SPA) for treatment of cancer has aroused interest because tumor regression and immunostimulation have been observed by several investigators (1-4). Feline leukemia virus (FeLV)-induced neoplasms (e.g., lymphosarcoma or leukemia) offer excellent models for the study of these phenomena. Tumor regression has been produced in a significant number of cats treated in our laboratory by ex vivo immunoadsorption using SPA over the last 4 years (5-7). Similar tumor regression had been observed previously (8)