Fibionectin, a known growth factor for fibroblasts, is produced by alveolar macrophages from patients with interstitial pulmonary fibrosis. Because peritoneal macrophages have been implicated in the disease process of endometriosis, we measured the production of fibronectin by peritoneal macrophages in vitro and the concentration of fibronectin in peritoneal fluid samples. Twenty-nine patients had a normal pelvis, 22 had endometriosis, and 14 had tubal occlusion and/or adhesions. Human peritoneal macrophages demonstrated de novo synthesis of fibronectin. The peritoneal macrophage fibronectin was detected by an enzyme-linked immunosorbent assay for serum fibronectin. Peritoneal macrophages from patients with endometriosis produced approximately three times the amount of fibronectin as normal patients or patients with tubal occlusion and/or adhesions (P≤ .01 and P≤ .02 respectively). The mean peritoneal fluid concentration of fibronectin, however, was about 30% lower in patients with endometriosis than in normal patients (P ≤.02). We suggest that increased peritoneal macrophage fibronectin production in patients with endometriosis may contribute to the adhesion formation and associated reactive fibrosis seen in this disease, and may also influence the implantation of endometrial cells and their subsequent growth in the pelvis.