Colorectal cancer is the third leading cause of cancer death in women. Studies on the potential protective effect of postmenopausal hormone replacement on the incidence of colon cancer have been contradictory. To attempt to clarify the potential protective effect of hormone replacement therapy (HRT), an English-language key word (KW) search of MEDLINE, up to August 1999, was performed for KW colon cancer or colorectal adenoma or colon adenoma or adenomatous polyp and KW estrogen replacement or hormone replacement. Additional references were obtained from reading of the reference lists. Thirty-five studies, including 3 meta-analyses, were found. Of these, 23 suggested any degree of protective effect of HRT, 11 reported neutral results, and 1 reported negative impact of hormone replacement. The single prospective randomized controlled trial included small numbers of inpatients taking high-dose estrogen. However, studies did not uniformly specify hormone type, dose, duration, and potential differential effects on right and left colon. Estrogen and progesterone effects were not often considered separately. Many studies had inadequate control of confounders, for example, family history of colon cancer or indication for endoscopy. Therefore, although the majority of studies, especially more rigorously designed recent studies, support the conclusion that postmenopausal estrogen replacement therapy (ERT) has a protective effect against colon adenomas and colon cancer, methodological limitations preclude practical application of study results at present. Prospective studies are needed to confirm the existence and degree of protective effect, as well as to specify the mechanism of protection.