A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8-1.8) for the lowest exposure category to 8.7 (95% CI 4.1-18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1-86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s.