Four of 8 baboons given sodium nitroprusside in a study of induced hypotension failed to recover normal arterial pressure after discontinuance of i.v. infusion; instead arterial pressure continued to decrease progressively and irreversibly. Other features noted in these animals were metabolic acidosis in both arterial blood and cerebrospinal fluid, and a markedly depressed cerebral oxygen uptake. In comparing this “non-recovery” group of animals with the other 4 baboons, in which arterial pressure recovered rapidly after discontinuance of nitroprusside infusion, it was found that the mean nitroprusside dose in the former was 4–6 times that used in the latter. The animals showing a “normal” response received doses of nitroprusside which, after correction for body weight, were similar to those used clinically. On the same weight correction basis, the smallest toxic dose in the baboon given over 1½–¾4 hours would be equivalent to 320 mg/hr in man and the mean toxic dose equivalent to 518 (SE 122) mg/hr. Caution is advocated in the use of high doses of sodium nitroprusside in patients who appear resistant to its hypotensive action. The appearance of a systemic acidosis may be an indication that the dose administered is nearing the toxic range.