The value for the slope of the left ventricular (LV) end-systolic pressure-dimension and pressure-volume relations has been proposed as a quantitative measure of the LV inotropic state. This measure of LV inotropic state is attractive because it is independent of preload and incorporates afterload. To investigate the sensitivity of the slope of these relations to alterations in contractile state, 10 normal subjects were studied using M-mode echocardiographic, phonocardiographic and indirect carotid pulse recordings during infusion of methoxamine to alter end-systolic pressure and during infusion of dobutamine (5 micrograms/kg/min) to increase LV inotropic state. Heart rate was maintained within a narrow range for each subject. End-systolic volume was calculated from end-systolic echocardiographic dimension by standard methods. End-systolic pressure was estimated from the dicrotic notch pressure determined from a calibrated carotid pulse recording; peak systolic pressure was also measured. Regardless of the method of approximating end-systolic pressure, the positive inotropic intervention caused a leftward shift in the end-systolic pressure-dimension and pressure-volume lines. With the dobutamine infusion, the value for the slope of the end-systolic pressure-dimension relation increased by 25% (range 16-46%, p less than 0.001), while the slope of the end-systolic pressure-volume relation increased by 55% (range 37-85%, p less than 0.001). In all cases, the curves were linear and became steeper with the positive inotropic intervention. In contrast, the value of the slope of the peak systolic pressure-end-systolic dimension relation showed a variable response to the dobutamine infusion (mean change 13%, range -77% to 73%; NS). Although the position of the peak systolic pressure-end-systolic dimension curve is consistently shifted with an alteration in inotropic state, the values of the slope of these curves are not reliable indicators of change in LV contractility. The values for the slope of the line relating end-systolic pressure (estimated by dicrotic notch pressure) to end-systolic dimension or volume, however, are highly sensitive to a change in inotropic state in human subjects.