The relation of colorectal cancer and its subsites with use of menopausal hormones was evaluated in the United States among 40,464 postmenopausal women, 41 to 80 years of age, who initially volunteered for a nationwide breast-cancer screening program and were followed for an average of 7.7 years. Ever-use of menopausal hormones was not associated with risk of total colorectal cancers (relative risk [RR] = 0.99, 95 percent confidence interval [CI] = 0.79-1.2) or cancers of the colon (RR = 1.1, CI = 0.81-1.6) or rectum (RR = 1.1, CI = 0.59-1.9). Recent hormone users, however, had a small nonsignificant reduction in risk of colorectal cancer (RR = 0.78, CI = 0.55-1.1), which was most pronounced for distal colon (RR = 0.68, CI = 0.29-1.6) and rectal tumors (RR = 0.64, CI = 0.24-1.7). No effect was observed for former hormone users, and risk generally did not vary by time since last use, type of regimen, or duration of use. However, the reduced risk for recent users was stronger for users of five or more years' duration. These data show some lowering of colorectal cancer risk among recent menopausal hormone users of long duration.