Regressing mouse Moloney sarcomas contain macrophages that are activated for tumor cell killing, while those found in progressively growing sarcomas either cannot kill or do so very poorly. Prostaglandin E2 (PGE2) has been shown to down-regulate macrophage activation in vitro. The study described here was designed, therefore, to ascertain and compare the concentrations of PGE2 in regressing and progressing Moloney sarcomas. Tumors were harvested for extraction and analyzed using conditions that minimized artifactual increases in PGE2 levels attributable to de novo synthesis. Concentrations of PGE2 were higher in progressing, compared to regressing, Moloney sarcomas during the early stages of tumor development. At nearly all time points, however, whether the neoplasms were of regressing or progressing type, the estimated concentrations of PGE2 in tumors exceeded the level that completely inhibits macrophage activation for tumor cell killing in vitro, that is, 10(-8) M. These data suggest either that PGE2 is not responsible for down-regulating activation in Moloney sarcomas or that, if PGE2 is responsible for the negative regulation of activation in progressing Moloney sarcomas, there must be something in regressing sarcomas that prevents the hormone from having its inhibitory effect.