This study was carried out in order to find out which part of the peritoneal wall reacts toward silica and produces peritoneal fibrosis. Colloidal silica was injected into the peritoneal cavity of rats to induce chemical peritonitis and frozen sections of the peritoneal wall were stained with specific antibodies toward type I and III collagens and fibronectin. A massive proliferation of granulation tissue was observed between the submesothelial and muscular layers within 48 hr visualized by prominent fibronectin staining. Type III collagen formed lamellar-like structures in the newly formed granulation tissue. The connective tissue reaction was extended into the underlying muscular tissue. Three weeks after silica injection the reactive granulation tissue exceeded the original peritoneum three- to fourfold in thickness. At this stage it contained extended fibrillar structures oriented perpendicular to the surface or muscular layers of the peritoneum. Type I collagen antibody was bound to the superficial cell layer in the control samples and in the early peritonitis whereas the entire granulation tissue was evenly stained at 3 weeks. Type III collagen antibody was bound to the surface layer of the peritoneum, granulation tissue, and perimysial connective tissue throughout the healing period. The results indicate that the peritoneal fibrotic process occurs under the thin peritoneal lining cell layer and on the surface of the muscle layer.