We investigated the association between hormone replacement therapy (HRT), primarily conjugated estrogens with or without medroxyprogesterone acetate, and colon cancer risk in a nested case-control study among women ages 55-79 years enrolled in Group Health Cooperative, a health maintenance organization in Washington state. Cases were diagnosed between 1984 and 1993. We selected controls randomly from enrollment files. HRT use was ascertained from a computerized database containing virtually all prescriptions dispensed since 1977. Among subjects with at least 5 years of pharmacy database information before reference date (1 year before diagnosis date), there were 341 cases of incident colon cancer and 1,679 controls. Estrogen use during the 5 years before reference date was not associated with risk of colon cancer [odds ratio (OR) = 0.85 and 95% confidence interval (CI) = 0.57-1.27 for 1-749 estrogen tablets; OR = 0.97 and 95% CI = 0.68-1.40 for > or =750 estrogen tablets]. An analysis including only women with at least 10 years of pharmacy database coverage found no association with use during the 10 years before reference date [OR = 1.07 (95% CI = 0.61-1.86) for 1-749 estrogen tablets; OR = 1.11 (95% CI = 0.69-1.80) for 750 or more estrogen tablets]. These results do not support the hypothesis that recent HRT use substantially reduces risk of colon cancer.