The fibrillar collagens, types I and III, have been demonstrated in healthy human gastric mucosa as well as in the submucosa of gastric ulcer edges, where they were found to be remarkably increased. In order to verify the occurrence and activity of de novo collagen synthesis, we examined gastric biopsy specimens from six patients with antral ulcers and six normal controls. By means of in situ hybridization, using a 35-S-labelled RNA probe, we could identify the specific procollagen mRNA for type I collagen. Fibronectin was stained immunohistochemically employing specific polyclonal antibodies. In normal gastric mucosa, procollagen type I mRNA was expressed by only a very limited number of cells while at the ulcer edges the specific signal could be demonstrated in a large number of submucosal cells. Fibronectin as marker of newly built connective tissue was found to be markedly increased in the submucosa of healing gastric ulcers as compared to normal controls. These results suggest a substantial role of fibroneogenesis in the process of gastric ulcer healing.