The goals of this study were to assess the association of diet, alcohol, smoking, and other life-style factors with the risk of colon and rectal cancer and to examine the differences in the risk factors associated with each cancer site. Information on diet, alcohol, smoking, and other life-style factors was obtained from 7945 Japanese-American men who were living in Hawaii and examined from 1965 through 1968. After 174,514 person-years of observation, 330 incident cases of colon cancer and 123 incident cases of rectal cancer were diagnosed by histology. The risk of both colon and rectal cancer increased with age, alcohol intake, and pack-years of cigarette smoking. For colon cancer, there was also a direct association with body mass index and heart rate, while an inverse association was observed with serum cholesterol, intake of monounsaturated fatty acid, and percentage of calories from fat. For rectal cancer, the risk decreased with an increase in the intake of carbohydrates as percentage of calories. These findings suggest that some of the risk factors for colon cancer are different from those for rectal cancer.