A family history of colorectal cancer is believed to place persons at increased risk for development of the disease. It is unclear, however, how "strong" a family history must be to increase this risk or to make colonoscopic screening appropriate. We performed initial colonoscopy in 154 asymptomatic subjects whose only suspected risk factor was one or two first-degree relatives with colorectal cancer; 48 of these subjects also had affected second- and third-degree relatives. We found 45 adenomas in 28 subjects (18%). One subject had a 3-cm villous adenoma. In 6 subjects, the most advanced findings were tubular adenomas 5-9 mm in diameter; in 21 subjects, we found only tubular adenomas that were 2-4 mm in diameter. The prevalence of adenomas increased significantly with age of subjects (p less than 0.01). Although the overall prevalence of colorectal neoplasms in our group was no greater than might be expected in the general population, subjects with two first-degree relatives tended to have more diminutive adenomas than those with one such relative. Our findings suggest that colonoscopy is not an appropriate first step in screening persons with one affected first-degree relative. For those with more complex family histories, more data are needed--particularly on the prevalence of advanced neoplasms--to determine whether a screening technique that is less costly and less invasive than colonoscopy may be adequate.