A new rapid and sensitive high-performance liquid chromatography (HPLC) method for the simultaneous determination of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine, 5-hydroxytryptamine (serotonin), 5hydroxyindoleacetic acid (5-HIAA), homovanillic acid and tryptophan has been developed and applied to mouse frontal cortex, caudate nucleus and dorsal raphe assays. A dual coulometric detector was used with detection at 0.25 and 0.55 V, which allowed the determination of tryptophan. Detection limits for all compounds (0.8-9.0 pg per injection, depending on the compounds) were useful for this application. Owing to great sensitivity of the method, the brain tissue samples can be very small, less than 2 mg. Linearity of standards was excellent (r b 0.999 in all cases). Intraday and interday precisions for samples analytes were generally acceptable (intraday assay CV 8.7% and interday assay CV 7.0% except for DOPAC and 5-HIAA, which was 11.4% for the low concentrations). Average recoveries of standard additions to sample analytes were b90%. Attention was paid to stability of standard and sample analytes when stored at 4ยฐC or at ร70ยฐC with two different homogenizing agents (0.1 M HClO 4 with 10 ร7 M ascorbic acid and 0.05 M HClO 4 without ascorbic acid). This simple, rapid and efficient method can be used as a basic research tool for modification of brain neurotransmitters in experimental pharmacological protocols for following psychotropic drug treatments in animals.