The large majority of mammalian retinal ganglion cells degenerate following section of their axons in the optic nerve. It has been suggested that some axotomized retina ganglion cells die because of toxic agents produced within their immediate environment. Our hypothesis was that nitric oxide might be one of the toxic factors implicated in the death of adult retinal ganglion cells post-axotomy. In the first instance, we determined whether there were any changes in the retinal expression of NADPH diaphorase both 3 and 14 days following intraorbital section of the optic nerve in adult rats. Secondly, if nitric oxide was indeed implicated in the death of ganglion cells, then trophic factors which rescue these neurons might do so by decreasing the expression of nitric oxide synthase. Recently, we found that a collicular proteoglycan purified from the major target of retinal ganglion cells, the superior colliculus, rescued a greater proportion of adult ganglion cells from axotomy-induced death than most other known trophic factors. We thus injected this proteoglycan intraocularly after section of the optic nerve and examined its effect on the expression of NADPH diaphorase in the retina. Thirdly, an inhibitor of nitric oxide synthetase was repeatedly injected into the eye following the section of the optic nerve in order to determine if such a treatment might improve the survival of retinal ganglion cells. The present results indicate that section of the optic nerve does not alter the overall levels of NADPH diaphorase within the adult rat retina. Intraocular injections of the collicular proteoglycan actually increased the number of neurons expressing NADPH diaphorase, particularly in the ganglion cell layer. Finally, inhibition of nitric oxide synthetase following axotomy resulted in increased loss of retinal ganglion cells over a 2 week period when compared with controls. Our findings indicate that, rather than being toxic, small amounts of nitric oxide may be important for the survival of a proportion of injured retina ganglion cells.