This research proposal is focused on the study of the selective effects of anticancer drugs on the hosts natural defense to tumors. The emphasis will be on identifying possible ways to pharmacologically modulate the murine natural killer system. The natural killer cell systems to be studied include spontaneous natural killer cells, cultured natural killer "like" cells, and in vivo augmented natural killer "like" cells (poly I/C, interferon). Comparisons will be drawn between drug effects on spontaneous natural killer cytotoxicity, and antibody dependent cellular cytotoxicity (against tumors) and between drug effects on natural killer cytotoxicity and in vivo protection against tumor growth. In addition, the effects of drugs on natural killer suppressor cells which modify the level of natural killer cytotoxicity will be studied. Drugs to be investigated include the alkylating agent cyclophosphamide and its metabolites phosphoramide mustard and 4-hydroxy cyclophosphamide and the anthracycline Adriamycin.