Fluoxetine is an antidepressant drug, a potent and specific inhibitor of serotonin reuptake (SSRI). Evidence suggests that being compared with tricyclic antidepressants, fluoxetine may cause significantly fewer anticholinergic, antihistaminergic and cardiotoxic side effects in the treatment of major depressive disorders. Chronic treatment with fluoxetine was not reported to affect the electrocardiogram (ECG). There is no clinical evidence of conduction delay and very little evidence of orthostatic hypotension. In the overdosed patients fewer cardiac symptoms were reported than with tricyclic antidepressants. However, dysrhythmia (atrial fibrillation and bradycardia) and syncope associated with fluoxetine treatment and overdose were reported. Although such reports have not been common, they do raise concerns. Thus we investigated the direct cardiovascular effects of the fluoxetine in isolated heart preparations and vessels of rats and rabbits. From 10(-6)M to 10(-4)M concentrations fluoxetine showed cardiodepressant and vasodilatory effects. These effects were similar to those of previously reported on tricyclic compounds. This review is a brief summary of possible cardiovascular effects of fluoxetine and other new SSRIs antidepressants from the literature based on experience of clinical studies and our experiments with fluoxetine on isolated rat and rabbit cardiac preparations and vessels. Possible explanations of the lower incidence of cardiovascular complications with fluoxetine in humans and cardiodepressant effects in vitro are discussed.