This report describes the action of ciguatoxin-1, the major ciguatoxin present in fishes that cause ciguatera, on the contractile activity of human cardiac musculature. Ciguatoxin-1 caused a large, sustained and concentration-dependent positive inotropy in human atrial trabeculae that were obtained during coronary artery bypass surgery from otherwise healthy hearts. Atenolol (a β1-adrenoceptor selective antagonist without local anaesthetic-type activity) or low concentrations of tetrodotoxin abolished the positive inotropy caused by ciguatoxin-1, indicating that ciguatoxin-1 stimulated neural elements present in this tissue to release noradrenaline. The positive inotropic action of ciguatoxin-1 did not stem from a significant direct action on myocardial voltage-dependent sodium channels, nor did it stem from significant α1- or β2-adrenoreceptor stimulation. Ciguatoxin-1 caused positive inotropy in preparations stimulated at between 0.02 and 2.0 Hz. Mannitol, currently the treatment of choice for ciguatera, did not significantly reverse the positive inotropy induced by ciguatoxin-1 in human atrial trabeculae.