Postmenopausal female hormone use has been associated with a reduced risk of colon cancer. We assessed the relation of use of these supplements to the risk of large bowel cancer. The data were collected in a case-control study of large bowel cancer conducted in Massachusetts. Control subjects were matched to incident cases of carcinoma of the colon or rectum on age, gender, and town precinct. The analysis was restricted to women who experienced a natural menopause or had had a hysterectomy with or without removal of the ovaries (292 colon cancer cases and 112 rectal cancer cases and their matched controls). Use of female hormone supplements was associated with a decreased risk of colon cancer among recent users (odds ratio, 0.6; 95% confidence interval, 0.4-1.0) and long duration (5+ years) of use (odds ratio, 0.5; 95% confidence interval, 0.3-0.9). The association with long duration of use appeared to be independent of recency of use and screening practices and was apparent for late-stage cancer. Hormone supplement use was not associated with a reduced risk of rectal cancer. Our results add to the evidence for a decreased risk of colon cancer associated with use of female hormone supplements.