To investigate the effects of peritoneal fluid from patients with endometriosis on mouse peritoneal macrophages (Mphi), peritoneal fluid from endometriosis patients (n = 15) were added to a monolayer of C3H/HeJ mouse peritoneal Mphi. Tumor necrosis factor-producing activity was measured by the L929 assay activated with FK-23 (a preparation of heat-killed Enterococcus faecalis). Tumor necrosis factor-producing activity of C3H/HeJ mouse peritoneal Mphi incubated with peritoneal fluid was suppressed in 14 endometriosis patients. Interestingly, in nine endometriosis patients, tumor necrosis factor-producing activity was much lower than seen with mouse peritoneal Mphi incubated with corticosterone. Peritoneal fluid contains suppressive properties for the activation of peritoneal Mphi, which might allow the implantation of free endometrial cells or the metaplastic phenomena stimulated by retrograde menstruation.