Colchicine can induce the malabsorption of vitamin B12 and other nutrients. Previous investigations have suggested but not proved that this malabsorption was due to a lesion in the ileal mucosa. Employing the receptor assay of M. Katz and B. A. Cooper (J Clin Invest 54:733-739, 1974), the authors have observed a dose-related, reversible reduction in the quantity of intrinsic factor-vitamin B12 (IF-B12) receptor (from 5.78 ng to 1.3 ng of B12 binding) in the intestinal mucosa of guinea pigs fed 0.05-0.25 mg/100 g colchicine/day for 3 days. Malabsorption of vitamin B12 was also demonstrated in vivo in similarly treated animals. Increasing intestinal motility with cascara sagrada had no effect on the IF-B12 receptor. The quantity of IF-B12 receptor and the amount of vitamin B12 absorbed increased markedly to greater than normal levels during recovery from a 3-day course of colchicine. The total number of intestinal cells decreased after colchicine administration and increased during recovery; however, the fluctuations observed were not sufficient to explain the changes in the quantity of receptor. Histologic examination of the ileal mucosa showed a decrease in the population of villus cells after colchicine. The correlation between the changes in receptor quantity and in vivo B12-absorption prove that the IF-B12 receptor is a critical limiting factor in B12 absorption.