Cytotoxic capacity of rat macrophages (M phi) and natural killer (NK)/natural cytotoxic cells (NC) against adherent growing, solid tumor-derived target cells was evaluated, modulating the activation status of effector cells and growth conditions of target cells. Testing a panel of target cells, cytotoxicity of NK/NC and M phi was strikingly correlated so that besides of target-cell binding structures basic lysability seems to be of influence with respect to cytotoxicity rates. Varying the in vivo growth conditions of target cells altered their lysability by M phi and NK/NC cells in the sense that ascitic versus subcutaneously (sc) grown tumors were more resistant to lysis. On the other hand, in vitro culturing did not influence susceptibility for M phi, but with some tumor lines increased lysis by NK/NC cells was observed. In the rat, the activation status of M phi and NC was not age-dependent, and NK cell activity only declined slowly with age. But cytotoxic potential of M phi obviously presents a strain characteristic, different from NK/NC cell activity, only the latter two correlating in different rat strains. Experiments to augment natural cytotoxic capacity revealed that application of Corynebacterium parvum (CP) activated M phi and NK/NC cells, while sc tumor implantation only resulted in increased NK/NC cell cytotoxicity, leaving M phi unaltered.