Seventy-five consecutive patients undergoing laparoscopy for chronic pelvic pain and/or infertility were studied to test whether beta-endorphin concentrations in peripheral mononuclear cells differed according to the presence or absence of endometriosis. Endometriosis was diagnosed in 45 subjects (minimal in 24, mild in 11, moderate in four, and severe in six). Twenty-eight women (62%) with endometriosis and ten (33%) without the disease reported moderate or severe pelvic pain. beta-Endorphin levels were lower in the endometriosis group than in the controls (16.6 +/- 11.2 versus 21.9 +/- 10.5 pg/10(6) cells; P less than .01). This decrease was attributable to reduced beta-endorphin concentrations in the endometriosis patients with moderate or severe pain compared with symptomatic controls (15.5 +/- 10.0 versus 26.3 +/- 7.0 pg/10(6) cells; P less than .01). A significant difference was also found in relation to the cycle phase: The opioid concentration was reduced in the luteal phase in the endometriosis group compared with controls (14.4 +/- 8.4 versus 23.8 +/- 7.5 pg/10(6) cells; P less than .01), but no differences were demonstrated in the follicular and periovulatory phases. beta-Endorphin is capable of modulating the immune response and can be considered as a classical cytokine. Low beta-endorphin production during the luteal phase may have implications in the development and/or maintenance of endometriosis.