The effects of the intravenously administered antidepressant drugs mianserin, imipramine, metapramine, nomifensine and amineptine against ischaemia and reperfusion arrhythmias were investigated in anaesthetized rats. Imipramine, metapramine, mianserin and high doses of nomifensine (0.5 mg·kg–1) reduced the mortality and the duration of ventricular fibrillation observed following coronary artery ligation. Amineptine was ineffective in preventing early postligation arrhythmias. With the tricyclic antidepressant drugs imipramine and metapramine, the arrhythmias were practically suppressed after 15 min following coronary artery ligation. The incidence of reperfusion arrhythmias was significantly reduced by tricyclic antidepressant drugs. In contrast, amineptine was not effective and did not alter cardiac function. It was suggested that nonspecific effects of these drugs account for their antiarrhythmic action. The most plausible explanation for their antiarrhythmic action may be a quinidine-like cardiac depressant activi