Acute poisoning induced by ciguatoxin or ciguatoxin-4c in male ICR mice was examined by light and electron microscopy. Target organs were the heart, medulla of adrenal glands, autonomic nerves and penis. There were no significant differences between the toxicity of ciguatoxin and ciguatoxin-4c. Either i.p. injection or oral administration (0.7 micrograms/kg) resulted in marked swelling and focal necrosis of cardiac muscle cells and effusion into the interstitial space of the heart. Degeneration of cells in the medulla of the adrenal glands was also observed. Continuous erection of the penis was observed in about 15% of the mice suffering from ciguatoxicosis. Although severe diarrhea was brought about by the administration of these phycotoxins, no morphological alterations were seen in the mucosa and muscle layers of the small intestine except in autonomic nerve fibers and synapses. Atropine suppressed the symptoms of diarrhea but had no effect on the injury to the cardiac muscle. Reserpine aggravated the clinical signs and pathological findings. Guanethidine and 5-hydroxy dopamine as well as those undergoing bilateral adrenalectomy had no significant effects on the ciguatoxicosis.