The effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamine release were investigated in superfused slices of rat striatum and hippocampus. MDMA (10 microM) increased the resting release of radioactivity from slices incubated in [3H]dopamine, [3H]5-hydroxytryptamine or [3H]noradrenaline. These effects of MDMA (10 microM) were blocked by the neuronal uptake inhibitors, cocaine (10 microM), fluoxetine (1 microM) and desmethylimipramine (1 microM), respectively. MDMA (10 microM) enhanced the stimulation-induced efflux of radioactivity from slices incubated in [3H]noradrenaline but not from slices incubated in [3H]5-hydroxytryptamine or [3H]dopamine. These results demonstrate for the first time a direct noradrenaline-releasing action of MDMA and differential effects of MDMA on the stimulation-induced release of noradrenaline, dopamine and 5-hydroxytryptamine from rat superfused brain slices.