The effect of age on brain histamine levels and histamine methyltransferase activity (HMT) was investigated. Male Sprague-Dawley rats (12 months old) displayed significantly higher hypothalamic, midbrain and cortical histamine concentrations than three-month-old animals. In contrast, HMT activity was significantly decreased in all three brain regions. The increase in brain histamine concentration of old rats could have been partially attributed to decreased activity of HMT since elevated levels of brain histamine are known to occur following HMT inhibition. Present results indicate that similarly to the reported changes in the concentration, synthesis and/or metabolism of other central neurotransmitters in old rats, brain histamine regulation may also be affected in the process of aging.