In the teleost retina the intercellular messenger nitric oxide can be synthesized by several cell types including cone photoreceptors and H1 horizontal cells, indicating a modulatory role within the outer plexiform layer, the first stage of the visual information processing. Therefore, the aim of this study was to elucidate the effects of nitric oxide on the physiology of cone horizontal cells in the intact retina. The nitric oxide donor sodium nitroprusside (0.5-2.5 mM) enhanced the light responsiveness of cone horizontal cells and reduced the degree of electrical coupling in the network. Furthermore, the spread of intracellularly injected Lucifer Yellow was restricted. The effects on light responsiveness and electrical coupling were qualitatively mimicked by 8-bromo-cGMP (0.5 mM) and could not be achieved by ferrocyanide (1 mM), the byproduct of nitric oxide liberation from nitroprusside. The effects of NO on the responsiveness of horizontal cells may be due to an action on green- and red-sensitive cones. Nitroprusside (0.1 mM) diminished the K(+)-stimulated release of endogenous dopamine by 50%, whereas the basal dopamine release was not affected, indicating that the effects on electrotonic horizontal cell coupling were not elicited by an NO-induced release of dopamine. With respect to the morphologic plasticity of the cone-horizontal cell synapse the inhibitor of endogenous nitric oxide synthesis L-nitroarginine (0.1 mM) had no influence on the formation or retraction of spinules. These results show that NO affects the responsiveness and coupling of the horizontal cell network in a dopamine-independent way.