Because imaging methods are unreliable for diagnosing or staging endometriosis, a definitive diagnosis requires surgery. The fact that the disease produces a local, and probably also a systemic, inflammatory process raises the possibility that a combination of inflammatory markers and cancer antigen-125 (CA-125) could make up a multiple-marker screening test for endometriosis. This possibility was tested in a case-control study of women of reproductive age having laparoscopy for a variety of reasons. Marker levels were compared in 63 women with operatively confirmed stage II-IV endometriosis and 78 others who were found surgically not to have the disease. The putative markers, estimated by enzyme-linked immunosorbent assays, were interleukin-6, tumor necrosis factor-α, macrophage migration inhibitory factor, macrophage chemotactic protein-1, interferon-β, leptin, and CA-125. The diagnostic performance of each of the 6 cytokines individually and of CA-125, based on receiver operating characteristic curves, was poor. After eliminating interferon-γ because levels were below the assay’s limit for detection, there was marked overlap in concentrations of the other 6 markers between the 2 study groups. The only markers whose levels were significantly higher in women with endometriosis were CA-125 and leptin. Evaluation of combinations of markers by classification tree analysis showed that a 3-marker panel of CA-125, macrophage chemotactic protein-1, and leptin predicted the presence of endometriosis in 51% of participants with 89% accuracy. Adding a fourth marker, macrophage migration inhibitory factor, diagnosed 48% of subjects with 93% accuracy. Using markers will not diagnose all patients as having, or not having, endometriosis, but disease status can be predicted with high accuracy in a substantial number of them, making diagnostic surgery unnecessary. The investigators believe that marker estimates will be an efficient adjunct to the work-up of patients suspected of having endometriosis.