Afterload reduction has become a routine treatment of patients with severe heart failure. In order to investigate the effect of afterload changes on indices of left ventricular performance, seven anesthetized dogs were studied. Serial alterations of afterload were produced with sodium nitroprusside and methoxamine infusions while the heart rate was maintained constant with right atrial pacing (120/min). High fidelity left ventricular (LV) pressure, aortic pressure (AoP) and systolic time intervals (STI) were measured simultaneously as a control and each time with the AoP changes. LV max dp/dt was measured by an RC differentiation and DP/DT was calculated from the pressure pulses and systolic time intervals. Each change in AoP resulted in a significant change in isovolumic pressure (IP) and the changes were parallel. Changes in pre-ejection period (PEP) and LV max (dp/dt)/(IP) were parallel changes in IP. A significant direct relationship was found between changes in IP and PEP, and an inverse relationship existed between changes in PEP and LV max (dp/dt)/(IP). Changes in LV max dp/dt and calculated DP/DT were parallel and approached unity. Thus, afterload changes with resultant changes in IP directly alter PEP and inversely affect max (dp/dt)/(IP). These effects of pure afterload changes must be considered in clinical pharmacologic studies when LV contractility is evaluated. Furthermore, calculated DP/DT can be used to measure changes in max dp/dt because of the close relationship between these two parameters.