The concentration in rat striatum of the meta and para isomers of tyramine and alpha-methyltyramine, after the administration of (+)-amphetamine, alpha-methyl-p-tyrosine (AMPT) and alpha-methylphenylalanine (AMPA) has been determined using chemical ionization gas chromatography mass spectrometry (c.i.g.c.m.s.). Twenty hours after the last of 7 daily injections of (+)-amphetamine (5 mg kg-1 i.p.) the concentration of alpha-methyl-p-tyramine in striatal tissue increased twofold compared to the concentration 20 h after a single injection. In contrast the concentration of alpha-methyl-m-tyramine did not change. alpha-Methyl-m-tyramine and alpha-methyldopamine were found in the striatum at concentrations of 42 ng g-1 and 13.5 ng g-1 respectively after treatment of rats 20 h before with AMPA (100 mg kg-1 i.p.). After treatment with AMPT (100 mg kg-1, 20 h before decapitation) only the para isomer of alpha-methyltyramine could be detected (13.7 ng g-1) although the striatal concentration of alpha-methyldopamine was 274 ng g-1, a level 20 times greater than that observed after AMPA treatment. The combined administration of both AMPT and AMPA (100 mg kg-1 each, 20 h) resulted in a reduction of the striatal concentration of alpha-methyl-m-tyramine but not alpha-methyl-p-tyramine. These data suggest that alpha-methyl-m-tyramine in rat striatum is formed by the enzyme tyrosine hydroxylase on substrate AMPA, rather than by ring dehydroxylation of alpha-methyldopa and alpha-methyldopamine. Significant reductions in the striatal concentrations of m-tyramine 2 h after the administration of AMPT, suggest that tyrosine hydroxylase is involved similarly in the production of m-tyramine.