We studied the immunosuppressive capacity of splenic lymphocytes from rabbits at different stages of progressive myxosarcoma induced by malignant rabbit fibroma virus (MV). Spleen cells taken from rabbits 7 days after virus inoculation proliferate poorly in response to Con A, and suppress normal responses to the mitogen. Those from animals 11 days after virus injection have recovered partially from MV-induced suppression. Further, their Con A responses are no longer suppressed by day 7 spleen cells. Supernatants from cultures of spleen cells from rabbits given MV 7 days previously suppress both antibody-producing and proliferative responses to unrelated antigens. Comparable supernatants from rabbits receiving MV 11 days before sacrifice neither suppress nor augment such responses. Mixing cells from 7 or 11 day MV rabbits with normal spleen cells gives similar results. When supernatants from spleen cell of rabbits with tumors induced 7 and 11 days previously are mixed, the supernatants from rabbits with 11-day-old tumors inhibit the suppressive capacity of those from animals with 7-day-old tumors. Similarly, mixing spleen cells from rabbits given MV 7 and 11 days previously results in culture supernatants that do not suppress normal antibody and proliferative responses. The ability of cells from rabbits given MV 11 days before to inhibit the effects of cells from rabbits given MV 7 days previously does not involve the production of interferon. Thus, despite progressive tumor burden, immunologic recovery is observed in rabbits 11 days after tumor virus inoculation. One factor in this recovery may be the generation of active inhibitors of virus-induced immunosuppression. Similar mechanisms may apply to recovery of immunologic function in other virus infections as well.