BACKGROUND: To date, only case reports or small studies have documented the syndrome of food-cobalamin malabsorption in specific populations of patients or situations. In this paper, we present the data from 80 unselected patients with cobalamin deficiency related to food-cobalamin malabsorption. METHODS: We studied 80 patients with well-established food-cobalamin malabsorption who were extracted from an observational cohort study (1995-2000) of 127 consecutive patients with cobalamin deficiency and who were followed in a department of internal medicine. RESULTS: The median age of patients was 66 years and the female to male ratio was 1.2. The mean hemoglobin level was 113+/-27 g/l (range 32-159 g/l) and the mean erythrocyte cell volume was 95.4+/-12.3 fl (range 55-140 fl). Mean serum vitamin B12 and homocysteine levels were 153+/-74 pg/ml (range 35-200 pg/ml) and 20.6+/-15.7 μmol/l (range 8-97 μmol/l), respectively. The main clinical findings noted were peripheral neuropathy (46.2%), stroke (12.5%), confusion or dementia (10%), asthenia (18.7%), leg edema (11.2%), and digestive disorders (7.5%). The commonest associated conditions were atrophic gastritis (39%) with evidence of Helicobacter pylori infection (12.2%) and alcohol abuse (13.7%). Three patients had Sjögren's syndrome and one had systemic sclerosis. Ten percent of all patients were on long-term metformin (10%) and 7.5% on acid-suppressive drugs. Correction of the serum vitamin B12 levels and hematological abnormalities was achieved equally well in all patients treated with either intramuscular or oral crystalline cyanocobalamin. CONCLUSION: This study suggests that food-cobalamin malabsorption may be the leading cause of vitamin B12 deficiency in adults. As other studies have also reported, the condition is often associated with neuro-psychiatric findings and with several other conditions. Oral and parenteral cobalamin appear to be equally effective in correcting serum B12 levels and hematological abnormalities and, in many cases, they also relieve symptoms.