We set out to investigate the possible beneficial effects on cognitive function of demented patients with cobalamin deficiency after cobalamin replacement. A total of 181 consecutive, demented (DSM-III or DSM-III-R criteria and score below 24 on the Mini-Mental State Examination [MMSE] outpatients (mean age 77.5 years) were prospectively evaluated and had their vitamin B12 level measured by radioimmunoassay. The frequency of vitamin B12 deficiency (less than 200 pg/mL) was 25% (46 patients). Treatment outcome was obtained in 19 patients (19 of 46). Despite cobalamin replacement, 16 of 19 patients persisted in showing progressive decline during follow-up visits (3 to 24 months). The nonresponse to vitamin B12 replacement in most cases seems to reflect the presence of associated irreversible dementia or a follow-up of shorter duration in a few patients. All of the patients who showed some improvement (MMSE returned to normal values) had mild dementia with a history of less than 2 years. Thus, screening for B12 deficiency should be considered in patients with recent onset of mild mental status changes.