Several aspects of stroma-free methemoglobin solution (SFMS) as a cyanide antidote were investigated using a rat model. Stroma-free methemoglobin solution was more than 90% effective against multiples of the LD90 of cyanide up to and including four times the LD90 and approximately 50% effective against multiples up to and including eight times the LD90. Highly concentrated solutions of SFMS (33 g/dl) did not differ significantly from less concentrated solutions of SFMS (16 g/dl) when compared on the basis of efficacy. Administration of large doses of SFMS alone resulted in no apparent morbidity or mortality. It could be that SFMS is a safe and effective alternative antidote for the treatment of cyanide poisoning.