The acute oral toxicity of palytoxin (PLTX), a highly toxic compound associated with seafood intoxication in tropical and subtropical areas, was investigated in mice. After gavage administration (300-1697 μg/kg) to groups of 5 female CD-1 mice, signs of toxicity and lethality were recorded for 24 h. The LD50 was 767 μg/kg (95% confidence limits: 549-1039 μg/kg) and the main symptoms observed were scratching, jumping, respiratory distress and paralysis. Hematoclinical analyses showed increased levels of creatine phosphokinase and lactate dehydrogenase at doses of 600 μg/kg and above, and aspartate transaminase at 848 μg/kg and above. Histological analysis revealed acute inflammation of the forestomach in mice surviving up to 24h after administration (424-1200 μg/kg). Other histological alterations were observed in the liver and pancreas, while cardiac and skeletal muscle cells revealed only ultrastructural alterations visible by transmission electron microscopy.