AbstractEvidence for cerebral B12 deficiency was searched for in 16 patients (age range 54–94 years) with subnormal serum B12 values (<110 pmol/l) with or without anaemia using sequential regional cerebral blood flow measurement (rCBF). Three patterns of responses followed B12 substitution in 11/16 cases: marked increase of the cerebral blood flow after one week (1); complete or partial normalization of regional decreases after one week (2) or after 1–3 months (3). Mental disturbances were observed in 14/16 patients and abnormally slow EEG activity in 11/12 patients before B12 substitution. During substitution a parallel clinical improvement was observed in 5/7 cases, who could cooperate in a follow‐up study, and normalization or marked improvement of the abnormal EEG activity was observed in three cases. We propose that rCBF is a valuable tool for diagnosis and follow‐up of this deficiency state. In addition, our results indicate that prophylactic B12 substitution should be considered at serum B12 serum values above the lower normal value especially in aged patients with coexisting organic brain