We suspected that patients with severe chronic heart failure may show hemodynamic changes after cardiac catheterization in the absence of drug therapy that could complicate assessment of the hemodynamic effects of new vasodilator and inotropic agents. To evaluate this phenomenon prospectively, hemodynamic variables were measured in 21 patients with heart failure 30 min and 2, 6, 24, and (in 12 patients) 48 hr after right heart catheterization, during which time therapy was not altered. During the first 2 hr we noted a significant increase in cardiac index and decreases in left ventricular filling pressure, mean arterial pressure, mean right atrial pressure, and systemic vascular resistance (p less than .01); a further decline in left ventricular filling pressure was noted over the next 24 hr, after which all hemodynamic variables remained stable. The magnitude of these hemodynamic changes resembled the effects of many established vasodilator drugs and was further enhanced after meals. These data indicate that hemodynamic improvement may be observed without any therapeutic intervention during the course of invasive studies in patients with severe chronic heart failure; such changes may lead investigators to attribute efficacy to ineffective drug therapy. To minimize the occurrence of such responses, we recommend that intravascular catheters be inserted the day before drug evaluation and that hemodynamic measurements be made with patients in a postprandial state.