A case-referent study was conducted in the province of Trento, Italy, to investigate the possible association between occupational exposure and scleroderma (systemic and localized variants).Twenty-one cases of scleroderma were ascertained from the computerized admission files of all of the local hospitals from 1976 to 1991. For each case, two age- and gender-matched referents were selected that were discharged from the hospital on the same day as the case. The subjects were interviewed with a structured questionnaire which included items for personal, work, and medical history. Exposure to organic solvents, other selected chemicals, silica dust, and hand-arm vibration was carefully investigated.A significant association was found between exposure to organic solvents (aromatic hydrocarbons) and scleroderma [odds ratio (OR) 9.28, 95% confidence interval (95% CI) 1.08-243.8]. For the men, the OR for exposure to silica was 5.20 (95% CI 0.48-74.1), whereas for the women it was 2.11 (95% CI 0.20-22.0) for exposure to other selected chemicals.The results of this case-referent study are consistent with those of previous case reports on the important role of occupation in the etiology of scleroderma. In particular, our findings confirm that exposure to organic solvents and silica is associated with this rare connective tissue disease.