AbstractBrain mitochondrial cytochrome oxidase and respiratory activities were compared afterin vivoandin vitroexposure to cyanide. For thein vivostudies, mice were exposed to a non‐lethal (4 mg kg−1) or lethal (20 mg kg−1) dose of KCN. From these mice, purified brain mitochondria were prepared and cytochrome oxidase and respiratory activities measured. Results of these experiments revealed greater inhibition of cytochrome oxidase activity following a lethal (20 mg kg−1) than a non‐lethal (4 mg kg−1) KCN dose (57 and 45% inhibition, respectively). Respiration states 3 and 4 of brain mitochondria prepared from mice that received 4 mg kg−1KCN were inhibted by 15 and 20%, respectively. In mice that received a lethal 20 mg kg−1KCN dose, respiration states 3 and 4 were each inhibited by ca. 30% (P50% inhibition of mitochondrial cytochrome oxidase activity, these findings suggest that a large proportion of cytochrome oxidase activity may be functional reserve and that cyanide poisoning likely involves other mechanisms in addition to