The persistence of the hemodynamic effects of prazosin was studied in 12 patients with chronic congestive heart failure. Multidose evaluation involving five 5-mg doses showed the initial decrease in systemic vascular resistance and increase in cardiac index, stroke work index, and stroke volume index to be transient. Doubling the dose did not restore effect. Modest decreases in pulmonary capillary-wedge and mean arterial pressures persisted throughout the study. In six patients, plasma prazosin concentration measured at times of hemodynamic observations showed the initial hemodynamic effect of prazosin to attenuate upon further administration despite mean plasma concentrations that exceeded those measured after the first dose. In patients with chronic heart failure, resting hemodynamic studies suggest a rapid attenuation of prazosin-mediated hemodynamic effect in the presence of adequate plasma concentration. Recognizing this phenomenon, if long-term prazosin therapy for congestive heart failure is contemplated, we suggest the hemodynamic response in individual patients be monitored.