A historical cohort study was conducted to investigate the long-term effect of exposure to ingested arsenic. The 454 residents who had been identified in a list made in 1959 were followed until 1992. They lived in an arsenic-polluted area, called Namiki-cho, Nakajo-machi, in Niigata Prefecture, Japan, and used well water containing inorganic arsenic. The exposure period was estimated to be about 5 years (1955-1959). Death certificates for the people who died between 1959 and 1992 were examined, and a total of 113 of the 454 residents were estimated to have drunk well water containing a high dose of arsenic (> or = 1 ppm). The standardized mortality rate ratios of these 113 residents were 15.69 for lung cancer (observed/expected = 8/0.51; 95% confidence interval (CI) 7.38-31.02) and 31.18 for urinary tract cancer (observed/expected = 3/0.10; 95% CI 8.62-91.75). Cox's proportional hazard analyses demonstrated that the hazard ratios of the highest exposure level group (> or = 1 ppm) versus the background exposure level group (0.001 ppm) were 1.74 (95% CI 1.10-2.74) for all deaths and 4.82 (95% CI 2.09-11.14) for all cancers. The analysis according to the skin signs of chronic arsenicism in 1959 showed that they were useful risk indicators for subsequent cancer development. In the development of lung cancer, there was evidence of synergism between arsenic intake and smoking habit.