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There was marked variation between p-hydroxylation and N-demethylation of methamphetamine in rats. Within 24 h, 10.4, 24-7 and 4.1% of the administered methamphetamine was excreted in urine unchanged, p-hydroxymethamphetamine (p-OH-MP, free plus conjugated) and also as amphetamine, respectively. Treatment by imipramine, desipramine, chlorpromazine, perphenazine and propericiazine 8 h before the administration with methamphetamine completely inhibited the urinary excretion of p-OH-MP whereas the excretion of amphetamine was enhanced by about 700 to 800%. This effect was also observed in rats treated with imipramine 16 and 24 h before methamphetamine. Phenothiazine and dibenzazepine derivatives reverse the degree of p-hydroxylation and N-demethylation of methamphetamine in-vivo in rats.