There have been few systematic studies of the non-malignant health effects of alpha-particle radiation in humans. Animal studies and a report on plutonium-exposed workers from Russia suggest an association between high doses to the lung from plutonium exposure and the development of fibrotic lung disease. Prompted by a case of lung fibrosis in a retired plutonium worker, we tested the hypothesis that plutonium inhalation increases the risk for developing chest radiograph abnormalities consistent with pulmonary fibrosis. We conducted a retrospective study of nuclear weapons workers that included estimating absorbed doses to the lung with an internal dosimetry model. Our study population consisted of 326 plutonium-exposed workers with absorbed lung doses from 0 to 28 Sv and 194 unexposed workers. We compared the severity of chest radiograph interstitial abnormalities between the two groups using the International Labour Organization profusion scoring system. There was a significantly higher proportion of abnormal profusion scores among plutonium-exposed workers (17.5%) than among unexposed workers (7.2%), P < 0.01. Lung doses of 10 Sv or greater conferred a 5.3-fold risk (95% CI 1.2-23.4) of having an abnormal chest X ray consistent with pulmonary fibrosis when compared with unexposed individuals after controlling for the effects of age, smoking and asbestos exposure. This study shows that plutonium may cause lung fibrosis in humans at absorbed lung doses above 10 Sv.