In severe congestive heart failure (CHF), abnormal reflex control of calf blood flow during brief head-up tilt that appears to normalize after transplantation (HTX) may be present during prolonged observation also. Therefore, we studied the effect of prolonged (30 min) 50° head-up tilt on calf skeletal muscle blood flow measured by the local ¹³³Xe washout method in CHF and after HTX and in patients with the presence vs. absence of native right atrium (+PNA and PNA, respectively). During brief head-up tilt, skeletal muscle blood flow increased 13 ± 42% in 9 severe CHF patients in contrast to a 28 ± 22% decrease (P < 0.01) in 11 control subjects, 24 ± 30% decrease in 15 moderate CHF patients (P < 0.05), 25 ± 14% decrease in 12 patients with recent HTX (P < 0.01), and 21 ± 24% decrease in 8 patients with distant HTX (P = 0.06). However, during sustained tilt, blood flow declined to similar levels of that in the other groups in severe CHF. HTX PNA vs. +PNA showed blunted skeletal muscle vasomotor control (P < 0.05) and a higher systolic blood pressure (139 ± 14 vs. 125 ± 15 mmHg, P < 0.05) and heart rate (92 ± 10 vs. 83 ± 8 beats/min, P < 0.05). Thus paradox vasodilatation of calf skeletal muscle in severe CHF is present only during brief but not prolonged tilt. This may be one explanation of the rare presence of orthostatic intolerance in CHF and implies only a minor possible role for the abnormality in edema pathogenesis. Removal of all right atrium in HTX has an important hemodynamic impact that may possibly affect later clinical outcome.