Despite considerable evidence implicating polyamines in CNS function, little is known about the status of the polyamine system in normal or abnormal human brain. We measured the levels of the polyamines spermidine, spermine and their precursor putrescine, in cortical and subcortical areas of 12 patients with Alzheimer's disease (AD). As compared with the controls, mean levels of spermidine were markedly and significantly increased (70%) whereas putrescine levels were decreased (28%) in temporal cortex of the AD patients. No other statistically significant changes were observed with the exception of a mean 35% reduction in spermine concentration in occipital cortex. In view of the modulatory effects of polyamines on calcium flux and glutamate receptor function, our data suggest that abnormal polyamine system activity may be involved in the neurodegenerative processes occurring in brain of patients with AD.