The possibility of pharmacological control of large bowel adenomas has been suggested by effectiveness of antioxidants in experimental tumor models and by the results of a limited clinical study using ascorbic acid. Over a two year period we tested this hypothesis in a randomized, double-blind study of 49 patients with polyposis coli. Of 36 patients who were evaluable at completion, 19 had received ascorbic acid, 3 g/day, and 17 had received a placebo. We found a reduction in polyp area in the ascorbic acid-treated group at nine months of follow-up (P less than 0.03) and trends toward reduction in both number and area of rectal polyps during the middle of the trial. A labeling study of rectal epithelium with tritiated thymidine also hinted at a treatment effect. Our data suggest that ascorbic acid temporarily influenced polyp growth or turnover. Although these results have no current therapeutic value, our findings support continued studies of chemoprevention in this and other high risk settings.