The effect of cimetidine on the absorption of orally administered crystalline or food (egg yolk-bound) vitamin B12 (B12) was studied in 13 patients. Absorption or crystalline B12 was normal and not significantly changed by cimetidine. In contrast, the uptake of food-bound B12 decreased in all patients, from a mean of 5.3% without the drug to 2.5% after it, a fall of 53% (p less than 0.0001). This impairment of B12 absorption raises the possibility that long-term, full-dose therapy with cimetidine may produce B12 deficiency similar to that seen in other hypochlorhydric states. Our data indicate that cimetidine-induced B12 malabsorption would not be detected by the standard Schilling test.