Individuals with a family history of colorectal cancer are believed to be at an increased risk of developing colorectal neoplasia. To estimate this risk and the potential yield of screening colonoscopy in this population, we recruited and prospectively colonoscoped 181 asymptomatic first-degree relatives (FDR) of colorectal cancer patients and 83 asymptomatic controls (without a family history of colorectal cancer). The mean ages for the FDR and control groups were 48.2 +/- 12.5 and 54.8 +/- 11.0, respectively. Adenomatous polyps were detected in 14.4 percent of FDRs and 8.4 percent of controls. Although 92 percent of our FDRs had only one FDR afflicted with colon cancer, those subjects with two or more afflicted FDRs had an even higher risk of developing colonic adenomas (23.8 percent) than those with only one afflicted FDR (13.1 percent). A greater proportion of adenomas was found to be beyond the reach of flexible sigmoidoscopy in the FDR group than in the controls (48 percent vs. 25 percent, respectively). Logistic regression analysis revealed that age, male sex, and FDR status were independent risk factors for the presence of colonic adenomatous polyps (RR = 2.32, 2.86, and 3.49, respectively; P less than 0.001). Those at greatest risk for harboring an asymptomatic colonic adenoma are male FDRs over the age of 50 (40 percent vs. 20 percent for age-matched male controls). Based on probability curves, males with one FDR afflicted with colon cancer appear to have an increased risk of developing a colonic adenoma beginning at 40 years of age. Our results document, for the first time, an increased prevalence of colonoscopically detectable adenomas in asymptomatic first-degree relatives of colon cancer patients, as compared with asymptomatic controls, and support the use of colonoscopy as a routine screening tool in this high-risk group.