We studied the risk of colorectal cancer in relation to serum cholesterol and beta-lipoprotein in more than 92,000 Swedish subjects less than 75 years old. The cohort was examined between 1963 and 1965 and followed by means of the Swedish Cancer Register until 1979. During this period, 528 colon cancers and 311 rectal cancers developed. A positive association was observed between the serum cholesterol level and the risk of rectal cancer among men (P less than 0.05), with a relative risk of 1.65 in men with levels greater than or equal to 276 mg per deciliter (7.1 mmol per liter). An association was also observed between the serum beta-lipoprotein level and the risk of rectal cancer among men (P less than 0.05). When cholesterol and beta-lipoprotein levels were considered together, they were associated with both rectal and colon cancer in men. The relative risk in men with both cholesterol greater than or equal to 250 mg per deciliter (6.5 mmol per liter) and beta-lipoprotein greater than or equal to 12 units (2.2 g per liter) was 1.62 for colon cancer (95 percent confidence interval, 1.18 to 2.22) and 1.70 for rectal cancer (1.18 to 2.44). Similar trends were observed in women, although they were not statistically significant.