Using pulsed Doppler echocardiography as a noninvasive method to assess central venous return, nine healthy volunteers were studied before and after isosorbide dinitrate given four times daily for 8 days. First dose isosorbide dinitrate led to a drop in heart rate and mean arterial pressure, and right ventricular inflow velocities decreased. With sustained treatment effects on systemic venous return remained unaltered, whereas reduction in heart rate and in mean arterial pressure was lost. Regarding this disappearing response as indicating a form of tolerance, venous hemodynamic nitrate effects were unaltered by development of tolerance on the arterial side.