Abstract In isolated Langendorff-perfused guinea pig hearts, an aqueous 1% potassium chloride solution, injected into the cannula, induced cardiac arrhythmias characterized by cardiac arrest alternating with ventricular extrasystoles. When imidazole was administered intraperitoneally in a dose of 5.87 mmol/kg, four hours prior to the experiment, an enhancement of the cardiac arrest was seen. In the same preparations, perfusion with a Krebs-Henseleit solution enriched with an aqueous 3% calcium chloride solution brought about arrhythmias that consisted of ventricular extrasystoles followed by a transient cardiac stop and then by the alternation of tachyarrhythmias with bradyarrhythmias. The heart stopped in cardiac arrest. Pretreatment with imidazole resulted in an obvious enhancement of the cardiotoxicity of calcium chloride. In ouabain-evoked (1.64 μmol/kg) cardiac arrhythmias, imidazole also had a proarrhythmogenic effect, accelerating the onset of arrhythmic events, including ventricular fibrillation. It also raised the percentage of ventricular fibrillations. These results are in contrast to our previous findings, which have shown that in anesthetized rats, the intracerebroventricular injection of imidazole had an antiarrhythmic activity. The causes of these discrepancies are discussed herein.