The increasing ratio of proximal to distal colorectal carcinomas was confirmed in this population-based study of 668 new cases diagnosed among Rochester, Minnesota residents between 1940 and 1979. The change was due to a rise in the incidence of proximal lesions (from 15.1 per 100,000 person-years in 1940-59 to 17.3 per 100,000 in 1960-79) and a simultaneous fall in the incidence of distal lesions (from 35.5 to 28.2 per 100,000 person-years). Changes in definitions or referral patterns played no role in these observations, although improved diagnostic capabilities may have had an impact on the incidence of proximal lesions. These discrepant changes in incidence strongly suggest that proximal and distal colonic cancers are different diseases or have a different pathogenesis. The changing incidence rates were not associated with consistent differences in clinical characteristics at the time of initial diagnosis.