The reported effects of nitric oxide (NO) on dopamine release from the striatum are variable and its precise effect on striatal nerve terminals is unclear. In the present study a novel method of applying NO to brain tissue in situ was employed. Photo-activation of Roussin's Black Salt (RBS), retained in isolated perfused brain tissue, was used to release NO at will upon illumination. Basal and electrically-stimulated dopamine efflux from the rat striatum in vitro was measured in real time using fast cyclic voltammetry. Illumination of an RBS pre-treated brain slice elicited a light intensity-related increase in basal dopamine efflux. Concomitantly there was a decrease in the level of electrically-stimulated dopamine efflux. Illumination in the absence of RBS pre-treatment had no effect on basal or stimulated dopamine efflux. The increase in basal dopamine efflux upon photo-activation of RBS was reduced by the presence of 10 microM oxyhaemoglobin, but was insensitive to the removal of extracellular calcium or the addition of 1 microM sulpiride. The decrease in electrically-stimulated dopamine efflux following illumination was not affected by the presence of either oxyhaemoglobin or sulpiride. It is concluded that NO, produced by photo-activation of RBS, releases dopamine from the rat striatum in vitro by a mechanism independent of extracellular calcium entry.