Amphetamine-induced release of previously accumulated [3H]dopamine ([3H]DA) was compared to the release of [3H]DA produced by unlabelled DA and fenfluramine. Like unlabelled DA, amphetamine was more potent than fenfluramine in releasing [3H]DA in all tissue preparations (untreated, pargyline-treated, and pargyline- and reserpine-treated corpus striatal slices). In tissue treated with both reserpine and pargyline, benztropine greatly reduced the efflux of [3H]DA produced by amphetamine and unlabelled DA but had only a slight effect on fenfluramine-induced release of [3H]DA. In the same tissue preparation, Q10 values for the release of [3H]DA produced by 3 X 10(-7) M amphetamine (1.8) and 3 X 10(-6) M unlabelled DA (1.7) were similar to that for the spontaneous release of [3H]DA (1.7). However, when the concentrations of amphetamine and unlabelled DA were increased to 10(-4) M, the Q10 values for the release of [3H]DA were diminished at the lower temperatures. These results suggest that amphetamine may release [3H]DA by two mechanisms: (1) by accelerated exchange diffusion due to its use of the DA uptake carrier to enter into neurons (this would predominate at low concentrations of amphetamine), and (2) by passive entrance into neurons and displacement of [3H]DA from binding sites (this would predominate at high concentrations of amphetamine).