The present study has investigated the effects of potassium, calcium and magnesium on ligation induced arrhythmias in the isolated rat heart. An attempt was made to elucidate the mechanism of action of potassium, however, more work is required to fully explain the action of this caution. Low calcium perfusion was found to reduce arrhythmias, however, calcium antagonists and magnesium, the physiological calcium antagonist, were only effective when they reduced the heart rate. Next, the possible roles of prostaglandins, lysophospholipids and free radicals in ligation induced arrhythmias in the isolated rat heart were studied. Exogenous ZK36374 and manipulation of endogenous prostaglandins did not seem to alter arrhythmias in this model. This lack of effect in vitro was attributed to the absence of blood and reflex neural influences. Similarly antioxidants, free radical scavengers and manoeuvres that would be expected to alter endogenous lysophospholipids did not alter arrhythmias in this model. Finally, 86Rb+ efflux was used to investigate the effects of the following compounds and conditions on potassium loss:- magnesium, pH, hypothermia, ligation, reperfusion, fibrillation induced by altering ionic milieu, calcium paradox, adenosine, mepacrine and chlorpromazine.