BACKGROUND. Although malignant mesothelioma is known to be strongly related to asbestos exposure, its relationship to familial factors is unclear. METHODS. We compared reported histories of cancer in first-degree relatives, obtained from telephone interviews with the next-of-kin of 196 patients who had a pathologic diagnosis of mesothelioma, and with those from 511 deceased controls. RESULTS. Among men exposed to asbestos, we found a statistically significant twofold elevation in the risk of mesothelioma for patients reporting cancer in two or more first-degree relatives. We found no significant elevation in women or among the small number of men without asbestos exposure. The next-of-kin of three patients (but no controls) reported a possible mesothelioma in a first-degree relative; asbestos exposure could not be ruled out in those relatives. Associations of asbestos with pleural mesothelioma were stronger among men with a reported family history of cancer than men without, although no statistical evidence of an interaction was detected. CONCLUSIONS. These results provide suggestive, but limited, evidence that a family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma given asbestos exposure. (C) 1996 American Cancer Society.