The susceptibility of cloned cell lines of the 13762NF rat mammary adenocarcinoma to macrophage-mediated cytolysis was investigated using both intra- and extratumoral macrophages. The percentage of Fc receptor-positive cells in tumors growing s.c. in syngeneic F344 rats ranged from 8 to 20%, but we could not demonstrate a significant correlation between the number of Fc receptor-positive cells within tumors and their spontaneous metastatic potentials. In macrophage-mediated cytolysis assays, cloned 13762NF cell lines of differing metastatic potential, established from tissue culture lines, fresh tumor explants, or short-term cultures (one passage in vitro), were used as targets. Effector cells were thioglycolate-elicited peritoneal macrophages (activated in vitro with bacterial lipopolysaccharide) or intratumoral macrophages (activated in vitro with lipopolysaccharide). When the effector cells were peritoneal macrophages, established cloned 13762NF cell lines showed little correlation in their susceptibility to macrophage-mediated cytolysis and metastatic potential, while this was not observed when fresh tumor explants were used. Highly metastatic MTLn3 cells were the least sensitive, less metastatic MTF7 and MTLn2 cells were more susceptible, and the low metastatic parental MTPa cells were the most sensitive in 72-h cytolysis assays. When the effector cells were intratumoral macrophages, all 13762NF cell lines showed less sensitivity in cytolysis assays than similar assays using thioglycolate-elicited peritoneal macrophages. With the exception of line MTLn2, short-term cultures (one passage in vitro) did not differ substantially in susceptibility to intratumoral macrophages compared to fresh explants. In this system, the sensitivity of 13762NF cells to macrophage-mediated cytolysis is a function of effector as well as target cell source.