Changes in the activity of brain glycolytic enzymes have been reported in Alzheimer's dementia. In this paper we studied the activity of the rate-limiting glycolytic enzymes, namely phosphofructokinase, lactate dehydrogenase and hexokinase in skin cultured fibroblasts and leukocytes from familial and sporadic Alzheimer's disease patients and unaffected relatives. Phosphofructokinase and lactate dehydrogenase activities were similar in all groups studied. The activity of hexokinase was reduced in some patients with the familial dominant form of Alzheimer's disease whilst it was normal in sporadic cases. These results suggest that Alzheimer's disease may be an heterogeneous disorder and that a modification on the catalytic activity of hexokinase may play a role in the pathogenesis of the disease in at least a subgroup of patients.