Two Antihistamines, terfenadine and astemizole have been withdrawn from major markets for the reason that these durgs have been reported to induce QT interval prolongation associated with the onset of Torsades do Pointes (TdP), resulting in a life-threatening ventricular arrhythmia. In this study, we investigated effects of diphenhydramine on electrocardiograms and hemodynamic parameters in conscious telemetered dogs. We validated and defined the sensitivity of the test system by monitoring basal parameters and using positive control substance, terfenadine. Single administration effects were tested during 24 hours for each test drug at dose 1 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg. We monitored QT, QTc, heart rate, blood pressure and body temperature after administering test drugs. In conscious telemetered dogs, diphenhydramine significantly prolonged $QT;(6.8\%;of;basal);and;QTc;(7.8\%;of;basal)$ at 100 mg/kg. Other parameters were not affected significantly. These findings suggest that antihistamines could induce important clinical relevance for patients taking excessive dosages of conventional antihistamines and those at risk of developing cardiac arrhythmias. Future studies that include other antihistamines and other classes will be necessary to predict the torsadogenic risk of drugs in humans.