We studied the in-vitro electrophysiologic effects of equimolar concentrations of cocaine and its metabolites on rat cardiac tissues. The effects on the sinus node rate were studied in spontaneously active sinoatrial preparations. The order of magnitude of the effects was: ethylcocaine > cocaine > benzoylecgonine and ecgonine methyl ester > ecgonine. The effects of cocaine and ethylcocaine were not additive. The actions of cocaine and ethylcocaine on membrane potentials were studied in papillary muscles driven at 5 Hz. Both compounds depressed to similar degrees the resting potential and the amplitude of the action potential, and increased the duration of the action potential. Simultaneous exposure to the two drugs did not result in effects greater than those of ethylcocaine or cocaine alone. It is concluded that (a) cocaine and its metabolites depressed the sinus node rate. Only cocaine and ethylcocaine exerted actions that may be of clinical significance. (b) Ethylcocaine had an effect greater than that of cocaine on the sinus node rate, and similar to that of the parent compound on ventricular membrane potentials. Thus, ethylcocaine may play a significant role in the cardiac electrophysiologic actions of cocaine, when the latter is used in combination with ethanol. (c) The effects of cocaine and ethylcocaine were not additive.