We report the effects of a tyrosine (and phenylalanine)-free amino acid mixture on tyrosine levels, ex vivo catecholamine synthesis and in vivo catecholamine release in brain regions of the rat. Administration of a tyrosine-free amino acid load reduced tissue levels of tyrosine (-50% after 2 h) in all brain regions examined (frontal cortex, hippocampus, striatum). The tyrosine-free amino acid mixture also reduced DOPA accumulation: this effect was most marked in striatum (-44%) and nucleus accumbens (-34%), areas with a predominantly dopaminergic innervation. Smaller decreases (-20-24%) were detected in other areas (cortex, hippocampus and hypothalamus). The effect on DOPA accumulation was prevented by supplementing the mixture with tyrosine/phenylalanine. The tyrosine-free amino acid mixture did not alter 5-HTP accumulation in any region. In microdialysis experiments, the tyrosine-free amino acid mixture did not consistently alter striatal extracellular dopamine under basal conditions but markedly, and dose-dependently, reduced the release of dopamine induced by amphetamine. In contrast, the tyrosine-free amino acid mixture did not alter either basal or amphetamine-evoked release of noradrenaline in hippocampus. Overall, these studies indicate that administration of a tyrosine-free amino acid mixture to rats depletes brain tyrosine to cause a decrease in regional brain catecholamine synthesis and release. Dopaminergic neurones appear to be more vulnerable to tyrosine depletion than noradrenergic neurones.