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Rats were injected intraperitoneally with lethal doses of sodium pentobarbital (115 mg/kg) or a lethal mixture of sodium salicylate (500 mg/kg) and sodium acetazolamide (25 mg/kg). Within about 20 min, part of each group was connected to an extracorporeal circuit containing uncoated activated charcoal and part to an empty control circuit. After a 90-min hemoperfusion, the treated groups showed a significantly decreased mortality (58% to 14% for pentobarbital; 100% to 0% for salicylate). Dogs were injected intravenously with lethal doses of sodium phenobarbital (175 mg/kg). One group was treated by hemoperfusion through an empty device in a control extracorporeal circuit, a second group was treated with loose-bed activated charcoal devices, and a third group with fixed-bed activated charcoal devices. For both the fixed and loose-bed devices, a 5-h hemoperfusion markedly decreased mortality (100% to less than or equal to 15%). The lethal combination of salicylate and closed-circuit methoxyflurane anesthesia was also successfully treated in dogs. This study clearly demonstrates the lifesaving potential of uncoated activated charcoal hemoperfusion.