After repeated ip and oral administrations of ciguatoxin (CTX) and ciguatoxin-4c (CTX-4c), one of the derivatives of CTX, to male ICR mice at a dose of 0.1 microgram/kg for 15 days, resulted in marked swelling of cardiac cells and endothelial lining cells of blood capillaries in the heart was observed. Single doses caused no discernible pathological changes. Damage to the capillaries was followed by prominent effusion of serum and erythrocytes into the interstitial spaces of the myocardium occurred. Swelling of the endothelial lining cells of capillaries caused narrowing of the lumen and accumulation of blood platelets in capillaries, which resulted in multiple single cell necroses of cardiac muscle cells. Within 1 month after the treatments of these phycotoxins, myocytes and capillaries appeared to be normal. Effusion in the interstitial spaces resulted in formation of bundles of dense collagen, which persisted for 14 months. Diffuse interstitial fibrosis was prominent in septum and ventricles, accompanied by bilateral ventricular hypertrophy. A single dose of 0.7 micrograms/kg ip resulted in severe acute heart injuries, followed by diffuse myocardial fibrosis.