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To test the efficacies of various antidotes to cyanide (CN) poisoning, the lethal dose of cyanide in dogs was estimated during constant infusion of potassium cyanide at a rate of 0.1 mg/kg/min. Additionally, arterial blood pressure, right ventricular pressure, heart rate, electrocardiogram, blood-gas and pH values, and whole blood and tissue CN concentrations were measured. The lethal dose in animals whose lungs were ventilated with room air was 2.4 ± .2 mg/kg (mean ± SE), while the whole-blood CN concentration was 438 ± 40 µg/dl and the gracilis muscle concentration was 2.0 ± .3 µg/100 g. A low dose of vitamin B12a (100 mg/kg), an infusion of thiosulfate (12 mg/kg/h), or ventilation with 100 per cent O2 increased the amount of CN needed to cause death. A bolus injection of nitrite (5 mg/kg), thiosulfate (150 mg/kg), or cysteine (450 mg/kg) increased the protection from lethality even further. Protection against CN administration for the total 150-min period of observation was provided by a bolus injection plus a constant infusion of nitrite (5 mg/kg bolus plus 5 mg/kg/h), (hiosulfate (30 mg/kg bolus plus 60 mg/kg/h), or vitamin B12a (50 mg/kg bolus plus 100 mg/kg/h). However, nitrite infusion produced high levels of methemoglobin 7.2 ±1.1 g/dl, while vitamin B12a infusion and cysteine injection, at the stated doses, did not prevent cyanide-induced circulatory failure. Therefore, thiosulfate appears to be the most effective and safest prophylactic agent against cyanide toxicity in dogs.