Between 1965 and 1985, 72 (64 male and 8 female) cases of multiple primary lung cancer (MPLC) in the National Cancer Center Hospital, Japan, were reviewed, and a retrospective hospital-based case-control study was performed with special reference to the patients' smoking and family histories. Control cases were selected from patients with unicentric lung cancer (ULC) with a longer survival time than that for other patients with whom they were matched for age, sex, histologic examination of primary lung cancer, and residence in prefecture. The overall percentage of MPLC was higher in males (3.1%) than in females (1.8%). Of the total number of cases, 46 were synchronous and 26, metachronous. The same histology was recognized in 38 cases (53%), and squamous cell carcinomas were observed in 65% of MPLC cases, all of whom were smokers. At least half of the MPLC found in nonsmokers were adenocarcinomas. Habitual smokers, with a Brinkman index (BI) of more than 50, accounted for 90% of all cases of MPLC, although 81% of the controls were also habitual smokers. A positive relationship dependent on the number of cigarettes smoked was observed between the BI of smokers and the proportion suffering MPLC. There was a family history of cancer in 47% of MPLC cases while, for controls, this figure was 40%. It was found that 67% of patients with MPLC and 61% with ULC were drinkers. The influence of cigarette smoking on MPLC was confirmed, especially in the cases of squamous cell carcinoma and small-cell carcinoma.