The effects of the opioid agonist dextromethorphan and the alpha 2-adrenoceptor agonist tizanidine on ouabain-induced cardiac arrhythmias were investigated in rats. Ouabain (10 mg/kg i.v.) elicited ventricular arrhythmias in all of the control rats. Administration of dextromethorphan (25 mg/kg i.v.) and tizanidine (0.1 mg/kg i.v.) 30 min before ouabain treatment significantly reduced the incidence of arrhythmias. We suggest that dextromethorphan and tizanidine showed these effects by decreasing excitatory amino acid (EAA) activity. It can be speculated that opioids and other EAA antagonists may have antiarrhythmic actions through both their central and peripheral effects as well.