Foreskin fibroblast cell lines from healthy subjects and patients with Alzheimer's disease or other neurological disorders have been analyzed for transketolase, by means of isoelectrofocusing and specific immunostaining. The enzyme profile in 70% of Alzheimer cell cultures exhibits alterations which are not encountered in controls and in other neurological diseases examined. Enzyme abnormalities most frequently observed were the appearance of new transketolase forms having unusually high alkaline pI. Experiments carried out with intact cells and with cell extracts treated with and without phenylmethyl-sulphonyl fluoride, suggest that the peculiar transketolase abnormalities observed in Alzheimer fibroblasts are due to enhanced proteolysis occurring in these cells rather than to intrinsic enzyme lability.