There has been a resurgence in the use of thalidomide over the past several years; however, little is known about its potential cardiac toxicity. Isolated, perfused guinea pig hearts were exposed to escalating concentrations of thalidomide or vehicle, and changes in RR interval, QT duration and QTc duration, and left ventricular inotropy and lusitropy comparing escalating concentrations of thalidomide with vehicle were sought. RR interval lengthened and QTc prolonged significantly at 10 microM concentrations. QT did not change. dP/dtmax increased and dP/dtmin decreased in response to thalidomide. Based on results using this preparation, thalidomide has a potential liability for lengthening QTc, but only at concentrations of 10 microM or greater. It possesses both positive inotropic and positive lusitropic properties.