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Abstract-The drug interaction between methamphetamine and quinidine/ cimetidine was investigated in terms of distribution of methamphetamine to the brain. The concentrations of methamphetamine and amphetamine in the brain after an s.c. Injection of methamphetamine were determined in rats pretreated with a single oral dose of quinidine or cimetidine.Both drugs markedly enhanced the increase in the concentrations of methamphetamine and its metabolite, ampheta mine. These results suggest that the recent finding of the enhancements of the behavioral effect of methamphetamine by quinidine and cimetidine is due to the increase in levels of methamphetamine and amphetamine in the brain by these pretreatment drugs.