BACKGROUND-The increased plasma disappearance of albumin has previously been described in decompensated congestive heart failure (CHF); this disappearance normalized after diuretic treatment. Cardiac transplantation (HTX) and current medical treatment affect microvascular structure and function. We investigated the plasma disappearance of albumin and the impact of microvascular thickness and electrostatic properties in patients with compensated CHF and after HTX. METHODS AND RESULTS-The fraction of intravascular albumin that passes to the extravascular space per unit time, as determined from the plasma disappearance of intravenously injected (131)I-labeled albumin, was increased to 7.8+/-1.7% in 16 patients with CHF compared with 18 controls (6.5+/-1.9%, P<0.05); these levels normalized after HTX (5.8+/-2.6%, P<0.01, n=17). The change in ratio between (131)I-albumin and simultaneously injected negatively charged glycosylated (125)I-albumin (selectivity index, >1/hour in controls) was lower in patients with HTX (0.993+/-0. 022/hour) than in controls (1.008+/-0.019/hour; P<0.05), which indicated a relatively increased plasma disappearance of negatively charged albumin in HTX patients. Capillary basement membrane thickness was evaluated semiquantitatively from skin biopsies and showed no difference in the 3 groups (control, CHF, and HTX patients). However, in all 3 study groups, subjects with thicker capillary basement membranes had lower albumin escape rates (6.1+/-1. 8%, n=32, versus 7.6+/-2.6% in subjects without thickening of capillary basement membranes, n=19; P<0.05). CONCLUSIONS-The plasma disappearance of albumin increased in patients with compensated CHF and it normalized after HTX. The present normalized capillary basement thicknesses in patients with CHF and the direct association between this parameter and plasma albumin disappearance indicate that previous compensatory microvascular basement membrane growth results in restricted permeability. Microvascular electrostatic properties did not relate to plasma albumin disappearance.