A lectin preparation containing enterokinase inhibitor purified or partially purified from red kidney bean (RKB) when fed to weanling rats was shown to cause small intestinal hyperplasia. To see if this hyperplastic effect on the rat small intestine was due to the mitogenic properties of the isolated lectin, male weanling rats were fed a chow containing 0.1% of the isolated lectin for six days. Age-matched control rats were fed regular chow. Both control and lectin-fed rats were sacrificed at one, two, three, four, and six days after the start of lectin feeding. The proximal small intestinal mucosa of rats fed lectin showed gradual increases in protein and DNA contents throughout the experimental period. Morphological studies showed marked increases in crypt depth from days 1 through 6 in these rats with essentially no change in mucosal thickness or villous height. DNA synthetic activity peaked at day 2, but was higher than control throughout the experimental period. Labeling index was 0.36 +/- 0.03 in duodenum of controls as compared to 0.45 +/- 0.02 in duodenum of weanling rats fed lectin for two days. These results demonstrate that RKB lectin stimulates overall DNA synthetic activity and increases crypt cell proliferation on the small intestine of weanling rats. The observed mucosal hyperplasia is probably due to increases in crypt cell population as shown by the increase in crypt depth.