The effect of methionine, an essential amino acid, on brain regional distribution of dopamine, serotinin and major acidic metabolites was studied in two genetically different strains of mice. These were the inbred albino BALB/C and the black C,,BL/6 mouse strains. The later strain was more sensitive than the former mouse strain to the methionine treatment. This has been demonstrated by methionine-produced change in dopamine metabolites in cerebellum, cortex and medulla regions, which suggests a decrease in dopamine turnover in the C,,BL/6 mice. Conversely, methionine-mediated changes in BALB/C mouse medullary region was suggestive of an increase in dopamine turnover. Little changes occurred in cerebral serotonin or 5-hydroxyindoleacetic acid levels, except for an increased serotonin in Cs7BL/6 mouse midbrain region. The results suggest that methionine possesses CNS pharmacological property pertaining to dopamine, other than its well-known action as a methyl donor in transmethylation processes, which is genotypic-dependent. Alternatively, modulation of the monoamines by methionine may explain its antidepressant property and possible contribution to the pharmacological hypotheses relevant to the biology of schizophrenia.