Hyperplastic polyps of the colon reveal a geographic distribution similar to that of colorectal cancer and adenomatous polyps. However, unlike adenomas--known precursors of colorectal cancer--little is known about the etiology or clinical significance of the hyperplastic polyp. In this prospective study, we set out to determine the main dietary and other lifestyle factors in the United States that might be associated with this lesion. Hyperplastic polyps of the distal colon and rectum were diagnosed in 219 of 12,922 men of the Health Professionals Follow-up Study having had an endoscopic procedure between 1986 and 1992, and 175 of 15,339 women of the Nurses' Health Study who had undergone an endoscopy for a variety of reasons between 1980 and 1990. After adjusting for age, family history of colon cancer, history of previous endoscopy, and total energy intake using multiple logistic regression, those consuming 30 g or more of alcohol per day were at increased risk relative to nondrinkers among men (relative risk [RR] = 1.69; 95 percent confidence interval [CI] = 1.01-2.80) and women (RR = 1.79, CI = 1.02-3.15). Current smoking also was found to be associated strongly positively with hyperplastic polyps in men (RR = 2.45, CI = 1.59-3.75) and women (RR = 1.96, CI = 1.16-2.86). High intake of folate was associated inversely with risk in both men (RR = 0.74, CI = 0.49-1.11, between high and low intakes of folate) and women (RR = 0.45, CI = 0.28-0.74, between high and low intakes of folate). Among macronutrients, a suggestive increase in risk existed with intake of animal fat, although this was attenuated in the full multivariate model (RR[men] = 1.48, CI = 0.94-2.41, and RR[women] = 1.22, CI = 0.77-1.94) between high and low quantities of animal fat intake. These prospective data provide evidence of associations between low folate intake, alcohol consumption, and current cigarette smoking, and risk of hyperplastic polyps of the distal colon and rectum. These same factors also have been found to be related to adenoma and cancer of the colon. The hyperplastic polyp is an indicator of populations at high risk for colorectal carcinoma, and it also may serve as a marker for factors that influence neoplastic evolution.