A growing body of evidence suggests that endometriosis modulates the microenvironment of peritoneal cavity. Therefore, in this study, we compared the protein profile of peritoneal fluids from normal fertile women with those from patients with infertility, and patients with mild to severe endometriosis. Two-dimensional gel electrophoresis of peritoneal fluids from normal subjects exhibited a distinct and reproducible pattern of proteins in the size ranges of approximately 35 to 80 kD and pI close to 4.5 to 6.6. Infertility without evidence of endometriosis was not associated with changes in the relative abundance of proteins present in the peritoneal fluid. However, mild endometriosis was associated with a mild reduction in the amount of several peritoneal protein spots with the approximate molecular weights of 35-40 kD and pI close to 5.7-6.0. These changes became markedly apparent in the peritoneal fluid of patients who suffered from the severe form of this disease. Severe endometriosis was also associated with appearance of protein spots in the gels that were not detectable in the peritoneal fluids of normal subjects. Consistent with these data, enzyme-linked immunosorbent assay showed that moderate to severe endometriosis was associated with markedly elevated levels of IL-10 in the peritoneal fluid. Reverse transcription followed by polymerase chain reaction amplification using primers specific to IL-10 confirmed presence of IL-10 mRNA in cells derived from peritoneal fluids. These findings show that endometriosis is associated with disturbed secretion of proteins into the peritoneal cavity and with an elevated level of IL-10 in the peritoneal fluid. The studies also show cells resident in peritoneum as a major source of IL-10.