A study of the possible modulation by nitric oxide (NO) of endogenous dopamine (DA) release was performed in bovine retina in vitro. NO synthase activity was measured in retinal homogenates and totally blocked by L-nitroarginine methyl ester (L-NA). Intact retinas were also exposed to hydroxylamine, an NO-generator which significantly decreased both basal and potassium-induced liberation of DA. In contrast, dibutyryl cGMP was ineffective. Furthermore, L-NA was able to increase basal DA release, its effects being potentiated in calcium free medium. Taken together, these results suggest that endogenous NO regulates DA release via cGMP independent mechanisms.