In this prospective study, the association between hematocrit values measured in 1965-68 and subsequent cancer incidence was studied among 7737 Japanese-American men in Hawaii. With an increase in hematocrit levels, there was an increasing risk for lung cancer, especially squamous or small cell type, and for kidney cancer. However, a statistically significant trend remained only for kidney cancer after adjusting for smoking history. The relative risk for kidney cancer was 4.94 (95% confidence interval, 1.03-23.63) for subjects with hematocrit values of 47 or higher compared with those with hematocrit values of 43 or lower. In contrast, the risk of oral-pharyngeal cancer decreased with increasing hematocrit levels. With adjustment for cigarette smoking and alcohol intake, the relative risk for oral-pharyngeal cancer was 0.20 (95% confidence interval, 0.04-0.88) for subjects with hematocrit values of 47 or higher compared with those with hematocrit values of 43 or lower. The association with kidney or oral-pharyngeal cancer was not affected by the time interval between examination and diagnosis of these cancers (< or = 10 and > 10 years). Erythropoietin production by kidney tumors and micronutrient deficiencies in oral-pharyngeal cancer cases may partially account for these results.