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Cyanide is a fast-acting toxicant that inhibits aerobic cellular respiration in mitochondria. Historically, amyl nitrite has been used to treat cyanide poisoning. The objective of this study was to demonstrate the effectiveness of intranasal (IN) administration of stabilized isoamyl nitrite (SIAN) against lethal potassium cyanide (KCN) intravenous (IV) challenge in a conscious nonhuman primate (NHP) model. Animals received an IV infusion of a 1 mg/mL KCN solution at a dose of 3.25 mg/kg for 15 min. The IN SIAN treatment was administered at 10 or 12 min post-start of KCN challenge and monkeys were monitored for survival, clinical signs, respiratory and cardiovascular changes via continuous telemetry recording. In addition, blood methemoglobin (metHb) levels and blood gases were closely monitored after KCN administration. Mid to mid-high doses (13.5 or 27.0 μL/kg) of SIAN treatments at 10 min post KCN challenge significantly increased animal survival. Improvements were also observed in respiratory and cardiovascular functions. The benefits of SIAN treatment decreased when treatment was delayed to 12 min post cyanide exposure. IN administration of SIAN 10 min following initiation of a lethal dose KCN infusion produced 100% survival (at doses ≥ 13.5 μL/kg) in NHP model of lethal cyanide intoxication.