BACKGROUND: Environmental asbestos pollution can cause malignant mesothelioma, but few studies have involved dose-response analyses with detailed information on occupational, domestic, and environmental exposures. OBJECTIVES: In the present study, we examined the spatial variation of mesothelioma risk in an area with high levels of asbestos pollution from an industrial plant, adjusting for occupational and domestic exposures. METHODS: This population-based case-control study included 103 incident cases of mesothelioma and 272 controls in 1987-1993 in the area around Casale Monferrato, Italy, where an important asbestos cement plant had been active for decades. Information collected included lifelong occupational and residential histories. Mesothelioma risk was estimated through logistic regression and a mixed additive-multiplicative model in which an additive scale was assumed for the risk associated with both residential distance from the plant and occupational exposures. The adjusted excess risk gradient by residential distance was modeled as an exponential decay with a threshold. RESULTS: Residents at the location of the asbestos cement factory had a relative risk for mesothelioma of 10.5 [95% confidence interval (CI), 3.8-50.1), adjusted for occupational and domestic exposures. Risk decreased rapidly with increasing distance from the factory, but at 10-km the risk was still 60% of its value at the source. The relative risk for occupational exposure was 6.0 (95% CI, 2.9-13.0), but this increased to 27.5 (95% CI, 7.8-153.4) when adjusted for residential distance. CONCLUSIONS: This study provides strong evidence that asbestos pollution from an industrial source greatly increases mesothelioma risk. Furthermore, relative risks from occupational exposure were underestimated and were markedly increased when adjusted for residential distance.