Nitroprusside is used acutely for the intraoperative induction of controlled hypotension and chronically for the control of hypertension, decrease of after-load and the treatment of vascular spasm. Dogs were given continuous infusions of various concentrations of sodium nitroprusside (SNP) and monitored for 48 h or until death. Dogs given 0.5 mg/kg per h did not have cyanide [CN] toxicity, achieving and maintaining blood Cn levels of about 2 .mu.g/ml. In animals given SNP, 0.75-1 mg/kg per h, blood cyanide levels increased progressively to above 7 .mu.g/ml and death occurred after 30-38 h. CN toxicity in these animals was evidenced early by progressive metabolic acidosis, increased mixed venous blood O2 tension and decreased O2 consumption. Dogs given SNP, 1 mg/kg per h, plus thiosulfate, 6 mg/kg per h, survived 48 h without evidence of CN toxicity and blood cyanide levels remained low (about 2 .mu.g/ml). Serum thiocyanate levels did not correlate with development of CN toxicity. The results are correlated with the events preceding a human fatality, which occurred after the requirement for SNP increased to between 0.5 and 1 mg/kg per h for 24 h, following prolonged infusion at a much lower dose. Results indicate that the dog is an acceptable model for study of SNP-related CN toxicity; chronic SNP administration should not exceed 0.5 mg/kg per h. Simultaneous thiosulfate administration affords protection against SNP-related CN toxicity; serum thiocyanate levels do not predict or reflect CN toxicity. Development of metabolic acidosis and increased mixed venous blood O2 tension best reflect development of CN toxicity.