The cardiac response to isoproterenol after propranolol withdrawal was studied in six normal persons. Serial isoproterenol infusions were done before and after oral propranolol administration, 160 mg daily for 2 days. Changes in electromechanical systole corrected for heart rate (QS2I) and pulse pressure were used to assess the inotropic response to isoproterenol, and changes in heart rate were used to assess the chronotropic response. As shown in previous studies, the negative inotropic effect of propranolol lasted only 12 to 15 h, while the negative chronotropic effect lasted 24 to 36 h. After the disappearance of blockade a hypersensitivity to isoproterenol was found 24 to 48 h after propranolol withdrawal in all three measured determinants. The explanation of this phenomenon most likely lies in the nature of adrenergic receptors that become activated during long-term blockade.