The efficacy of orally administered alpha-ketoglutarate (AKG), alone and in combination with n-acetyl-cysteine (NAC), in reducing the lethal effects of injected potassium cyanide was examined in the mouse. A behavioral scoring system was developed to monitor and measure the signs of toxicity associated with cyanide exposure. AKG significantly reduced the lethality of KCN (6.7 mg/kg ip) in a dose-related manner. The protective effect of AKG was observed if given between 10 and 30 min prior to cyanide exposure. NAC increased the protective effect of AKG but did not alter the time course of protection. AKG alone or in combination with NAC significantly reduced the duration of the toxicity associated with cyanide exposure. This study identifies AKG as an orally effective cyanide antagonist. The protective effect of AKG is enhanced by concomitant administration of NAC. Our work also describes a scoring system which quantifies the signs of toxicity associated with cyanide poisoning.