Thirty-seven individuals with an increased lifetime risk of colorectal cancer because of family history and a control group (n = 21) with no such family history underwent colonoscopy. No neoplastic lesion was found in any individual. Rectal biopsies of macroscopically normal mucosa were taken 8 cm from the anal margin and mucosal proliferation assessed by the crypt cell production rate (CCPR). There was no difference in CCPR between the control group (median 10 (95 per cent confidence interval 7-11) cells per crypt per h) and those at intermediate risk (lifetime risk between 1:17 and 1:10, n = 14). However, there was a significant difference in CCPR between the control group and those at higher risk (lifetime risk > 1:10, n = 23) (median CCPR 13 (95 per cent confidence interval 10-17) cells per crypt per h, P = 0.004). A high risk of colorectal cancer derived from family history correlates with an increased colorectal mucosal proliferation rate.