Iron plays an important role in maintaining normal brain function. However, in many neurodegenerative diseases abnormal iron accumulation in specific brain regions has been consistently reported. In this study, we investigated the neurotoxic effect of the intracerebroventricularly injected iron on the cerebellar Purkinje cells in the rat and the role of nitric oxide (NO) in this process. The role of NO in rats administered iron (FeCl36H2O) was examined with the use of a donor of NO, L-arginine (L-Arg) and a central selective inhibitor of NO synthase, 7-nitroindazole (7-NI). For this reason, rats were divided into 5 groups: control, iron-injected, iron plus L-Arg, iron plus 7-NI, and iron plus L-Arg plus 7-NI. Means (value +/- standard deviation) of the total numbers of Purkinje cells in the cerebellum were estimated as 337 +/- 23, 209 +/- 16, 167 +/- 19, 305 +/- 26, and 265 +/- 14 thousands in the control, iron, iron plus L-Arg, iron plus 7-NI, and iron plus L-Arg plus 7-NI groups, respectively. Iron treatment alone and the combination of iron and L-Arg caused a significant reduction in the total number of cerebellar Purkinje cells. Therefore, L-Arg increased the Purkinje cell loss induced by treatment with iron. These data show that inhibition of the neuronal NOS by 7-NI can prevent some of the deleterious effects of iron on cerebellar Purkinje cells. Presence of L-arginine decreased the neuroprotective effect of 7-NI.