Four compounds: amodiaquine, quinacrine, 1,4-(tele)-methylhistamine and metoprine, which in vitro effectively inhibit histamine N-methyltransferase (HMT) activity, were tested for their effects on histamine (HI) levels in the rat brain and ex vivo HMT activity. In in vitro studies all these compounds at concentration of 10 microM produced complete inhibition of HMT activity. Amodiaquine, quinacrine and 1,4-(tele)-methyl-HI weakly inhibited HMT activity ex vivo and they failed to alter HI levels in the rat brain. Of the tested compounds only metoprine significantly increased brain HI levels in both normal rats and 1-histidine treated rats. Metoprine and, to much lesser degree, amodiaquine, but not aminoguanidine, slowed down the disappearance of exogenous HI from the rat brain. It is suggested that metoprine, because of its simultaneous capability of inhibiting HMT activity and increasing brain HI level, might be a useful pharmacological tool in studies of HI metabolism and neurotransmission in the central nervous system.