The effects of intravenously injected 4-dimethylaminophenol-HCl (DMAP), Co2EDTA, and Co(histidine)2 on the survival rate and several physiological parameters were studied on dogs after acute intravenous poisoning with the double lethal dose of potassium cyanide. All dogs survived when the antidotes were administered 1 min after poisoning. When the therapy began 4 min after poisoning more dogs were rescued in the DMAP group than in the cobalt groups. DMAP, Co2EDTA, and Co(histidine)2 restored circulation and respiration of the surviving animals in a similar manner. The increase in the plasma concentrations of glucose and lactate was much higher in the Co2EDTA group than in the DMAP group. The injection of Co2EDTA produced a sharp rise in the lactate-to-pyruvate ratio. The lactate-to-pyruvate ratio stayed unchanged for some 15 min after injection of DMAP before also rising. The total dose of KCN (4 mg/kg) was bound to the ferrihemoglobin formed by DMAP. The arterial pO2 increase, caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin, was less when the cyanide could act on the tissues for a longer period of time before the therapy with DMAP began. DMAP is more appropriate for the therapy of cyanide poisoning than Co2EDTA, since the latter adds its inhibitory effects on the metabolism to those of cyanide.