BACKGROUND: There is a need for a reliable marker of endometriosis, especially in early stages of peritoneal disease during which imaging is not effective. The use of serum interleukin (IL)-6 as a marker is controversial. To readdress the matter, patients undergoing laparoscopy were prospectively evaluated for serum IL-6 levels. MATERIALS AND METHODS: A total of 119 women 31 years old who underwent laparoscopy were divided into groups: control patients (n = 38) with no pathologic findings; endometriosis sufferers (n = 47) with minimal-mild (MM, n = 11) or moderate-severe (MS, n = 36) endometriosis; uterine myomas (n = 13) and benign ovarian pathologies (n = 21). Blood was drawn on cycles days 5-12 and stored for subsequent analysis of IL-6 and carbohydrate antigen (CA)-125 levels. RESULTS: Serum IL-6 levels were significantly (P = 0.002) higher in women with MM endometriosis (29.4 ± 9.0 pg/ml) than in controls (15.7 ± 9.3 pg/ml). When all the non-endometriosis patients were grouped together (n = 72) and serum IL-6 (17.8 ± 12.1 pg/ml) compared with MS (n = 36; 17.6 ± 10.3 pg/ml) and MM (n = 11; 29.4 ± 9.0 pg/ml) endometriosis significantly (P < 0.01) higher levels in MM endometriosis were observed as compared to the other two groups. Serum Ca-125 levels were significantly (P < 0.01) elevated in MS endometriosis. A serum IL-6 threshold of 25.75 pg/ml afforded a sensitivity of 75% and specificity of 83% in the diagnosis of MM endometriosis. Sensitivity and specificity for CA-125 in the diagnosis of MS endometriosis, using 35 IU/ml as the cut-off value, were 47% and 97%, respectively. CONCLUSIONS: IL-6 is a reliable non-invasive marker of MM endometriosis, whereas Ca-125 is of use as a marker of severe cases.