The aim of the study was to examine the changes in left ventricular (LV) relaxation rate induced by variations in inotropic state. Eight normal subjects and 29 patients with coronary artery disease (CAD) were studied. First, we used interventions that increase myocardial calcium influx (atrial pacing or postpacing beat) or decrease it (intracoronary injection of nifedipine). Relaxation rate was estimated from the time constant (T1) of isovolumic LV pressure fall during the fist 40 msec after peak negative dP/dt. Under basal conditions, T1 was impaired in CAD patients (58 vs 43 msec; p less than 0.01), despite similar heart rate, LV pressures and peak positive dP/dt (1620 vs 1787 mm Hg/sec; NS). During atrial pacing at 135 +/- 7 beats/min, peak positive dP/dt increased to 2220 mm Hg/sec in 11 CAD patients and to 2256 mm Hg/sec in eight normal subjects. T1 decreased more in CAD patients than in normal subjects (17 vs 7 msec; p less than 0.01). T1 changes also differed in the postpacing beat between CAD patients and normal subjects (-6 vs 5 msec; p less than 0.01) or when nifedipine was injected during the pacing (4 vs 20 msec; p less than 0.01). Intravenous calcium injection during atrial pacing in another group of 18 CAD patients further improved peak positive dP/dt and T1 (-3 msec; p less than 0.05) and normalized the changes in relaxation during the postpacing heart. Our data indicate that a variable coupling between LV inotropic state and relaxation rate exists in man during changes in calcium influx and that this coupling is abnormal in CAD patients.