A geographical cluster of scleroderma and scleroderma-related features was identified in a rural area in the province of Rome. Two patients with scleroderma, three with CREST syndrome and one with eosinophilic fasciitis were living in a village where the total population included 572 persons of voting age. No kindred relationships were demonstrable among these patients. Clinical features of scleroderma such as Raynaud's phenomenon, bilateral hand edema, and digital scars were detected in an additional 10 cases. A group of apparently healthy subjects with scleroderma-related serological abnormalities (circulating antinuclear and anticentriole autoantibodies) was also identified in the village. No disease-associated HLA antigen in the patients nor genetic differences between patients and healthy subjects living in the same village were detected by HLA typing. Some still unidentified environmental factors acting on genetically predisposed subjects may be responsible for the clustering of the disease seen in this study.