The effect of an unloading (nifedipine, 20 mg sublingually) and of a combined unloading and positive inotropic intervention (nifedipine plus digoxin, 0.5 mg intravenously) on left ventricular performance was assessed in 48 patients with chronic severe aortic insufficiency. The left ventricular pump function-myocardial contractility relation (ejection fraction, EF vs. peak arterial pressure to end-systolic volume ratio, PAP/ESV), and the pump function-afterload relation (EF vs. mean systolic wall stress, MWS) were constructed by means of quantitative M-mode and two-dimensional echocardiography. In patients with normal control pump function (n = 14), nifedipine markedly decreased MWS, moving the patients to a new, more advantageous EF-MWS relation. In the 34 patients with abnormal pump function, the myocardial contractility level was the mean factor conditioning the response to pharmacological intervention. Patients with a value of PAP/ESV greater than 2.5 (n = 22) had normalization of EF after nifedipine and were upgraded to a more advantageous outlook for left ventricular mechanics EF-MWS and EF-PAP/ESV relations. Of the 12 patients without normalization of EF after nifedipine, only the 4 patients with PAP/ESV greater than 2 had normalization of pump function indices after combined administration of nifedipine and digoxin.