Peritoneal fluid from women with endometriosis, unexplained infertility, and fertile controls were compared to one another and to normal human serum for effects on lymphocyte proliferation in vitro. Peritoneal fluid samples were also assayed for both interleukin-1 and interleukin-2. All peritoneal fluid samples significantly enhanced lymphocyte proliferation in both mitogen-stimulated and unstimulated cultures compared with serum controls. Mitogen-induced leukocyte proliferation was higher in the presence of peritoneal fluid from women with endometriosis compared with other samples. Five out of 23 samples from endometriosis patients contained elevated levels of interleukin-1 and three out of 23 contained elevated levels of interleukin-2. Six out of eight peritoneal fluid samples from unexplained infertility patients also had elevated levels of interleukin-2; samples from fertile women did not contain elevated levels of either cytokine. Our data indicate that peritoneal fluid from women with endometriosis and unexplained infertility support the activation and proliferation of lymphocytes. Leukocyte products may locally affect the progression of disease and fertility.