Supernatant was produced from activated peritoneal polymorphonuclear leucocyte-rich cell populations from different strains of mice. These supernatants were studied for their ability to modify spontaneous and mitogen-induced blastogenesis of syngeneic and allogeneic splenocytes. Our results indicate that polymorphonuclear leucocyte-rich cell cultures from two strains of mice, A/J and BALB/c, produced a supernatant that could enhance PHA-induced blastogenesis of syngeneic and allogeneic splenocytes. Cells from a third strain C57B1/6, did not produce an active supernatant. In general, the response by splenocytes from these three strains paralleled the production of active supernatant that we observed. The response to the active supernatant was dependent upon the mitogen stimulation of the splenocytes, the mitogen dilution and the supernatant activity. These functions are believed to be genetically determined.