Cardiovascular toxicity of palytoxin (PTX), isolated from Palythoa tuberculosa, was examined in pentobarbital-anesthetized dogs. In intact dogs, PTX at doses below 0.05 microgram/kg i.v. caused a sustained rise in arterial pressure. PTX at doses above 0.06 microgram/kg i.v. caused a transient rise in arterial pressure followed by rapid hypotension and resulting in death within 5 min. In open-chest dogs, a sublethal dose of PTX caused constriction of coronary, femoral and renal arteries. Renal blood flow was interrupted by a sublethal dose of PTX. PTX at a dose of 0.04 microgram/kg, which was lethal for this preparation, caused a rapid interruption of renal and coronary blood flows. Total peripheral resistance increased and cardiac output fell abruptly at this dose. It is suggested that PTX exerts its toxic action through intense vasoconstriction in the whole body, particularly in the coronary and renal vascular beds, and through depression of the cardiac function.