In a multicenter study of lung cancer in lifetime nonsmokers in the United States, 646 female lung cancer patients and 1,252 population controls were interviewed regarding history of cancer in their first-degree relatives. A 30% increased risk (95% confidence interval 0.9-1.8) was found for a history of respiratory tract cancer in parents or siblings after adjustment for exposure to environmental tobacco smoke (ETS) in adult life. Lung cancer, which represented approximately two thirds of the respiratory tract cancers, occurred more frequently in first-degree relatives of lung cancer patients than in comparable relatives of population controls (ETS-adjusted odds ratio = 1.29, 95% confidence interval 0.9-1.9). In particular, a significant threefold increased risk for lung cancer was associated with lung cancer diagnosed in mothers and sisters. The increased risk in relation to family history of lung cancer was observed among parents and siblings who were smokers as well as in those who were nonsmokers. The association with family history of lung cancer was strengthened when the analysis was restricted to adenocarcinoma of the lung (ETS-adjusted odds ratio = 1.50, 95% confidence interval 1.0-2.2). However, there was no association between family history of other cancers and risk of lung cancer in nonsmokers.