Immunomodulators were incorporated in the L2C guinea pig leukemia model following chemotherapy with MeCCNU to augment and stimulate the host immune response. Treated animals developed a strong tumor rejection immunity and became refractory to subsequent tumor challenge. Staphylococcus aureas protein A (SPA) possesses the ability to bind immunoglobulin Fc antibody portions. SPA has been shown to (1) increase antibody dependent cell cytotoxicity responses, (2) augment or inhibit a primary delayed hypersensitivity response in vivo, and (3) suppress cellular DNA synthesis in mitogen activated and transformed cells. Recent studies have examined the effect of nystatin on the tumoricidal activity of M phi in vivo. Results demonstrated an increase in phagocytic and tumoricidal activity concomitant with an increase in T and B cell activity. Soluble tumor antigens, obtained from the surface of the L2C leukemia, have been characterized. Both KCl and LDS extracts were capable of protecting guinea pigs against a viable challenge of L2C leukemia cells. Immunological studies of TPA induced guinea pig leukemias are in progress to discern their relationship to the established and well-characterized L2C leukemia.