Studies were initiated to determine if it was possible to use a tumorbearing animal's own spleen cells to impart resistance to its neoplasm. YC8 T-cell lymphoma-bearing BALB/c mice (TBAs) were immunized with allogeneic DBA/2 spleen cells, which share cross-reacting antigens with the YC8 tumor. Animals immunized with the alloantigen were splenectomized and their spleen cells co-cultured with additional alloantigens for 2 days in media containing 2% polyethylene glycol (PEG) before being returned to the cyclophosphamide (cytoxan) (Ctx) pretreated autologous host. Treatment with Ctx was used to reduce suppressor factors in the TBA. It was found that when cultured spleen cells were returned to the autologous TBA, much greater resistance was imparted to the host and, in many instances, regression of the YC8 tumor was observed. © 1994 Raven Press, Ltd., New York.