Sodium nitroprusside (SNP) significantly decreased basal dopamine (DA) release when rat striatal slices were incubated in a physiological medium deficient in antioxidants. Depolarization-induced DA release (KCl 25 mM), which was accompanied with a 85% decline in tissue DA levels, was also inhibited by SNP and hydroxylamine (HA). Contrary to these findings, SNP did not protect the slices against depolarization-induced DA depletion. With HA, moreover, tissue DA levels were found to be depleted more than the control levels, indicating that DA, which is released from or stored in the slices, might be converted to an undetectable product under these conditions. Supporting this conclusion, incubation of the DA standards with SNP caused a dose-dependent loss in DA levels, an effect that was reversed partially by oxyhemoglobin and inhibited completely by antioxidants. Consistently, both SNP and HA, but not L-arginine, significantly increased basal DA release when striatal slices were incubated in antioxidants-containing medium. These results indicate that nitric oxide (NO), which is generated from SNP and HA by different mechanisms, stimulates DA release from rat striatal slices. Observation of this effect, however, requires the presence of antioxidants in the medium.