Incubation of a primary culture of rat striatal neurons with sodium nitroprusside (SNP), a known source of nitric oxide (NO), showed a concentration-dependent increase in cyclic GMP levels with an EC50 value of 13.7 microM. Twenty-four hours following incubation with 10 microM SNP, striatal neurons underwent degeneration as assessed immunohistochemically and biochemically. In contrast, potassium ferricyanate at concentrations up to 1 mM had no effect on striatal neuron viability. These results indicate that SNP has neurotoxic actions in-vitro, an effect that may involve NO as a second messenger.