We tested the hypothesis that albumin reduces the vascular wall hydraulic conductivity by an interaction with the endothelium. The system consisted of luminal and abluminal chambers separated by a microporous filter onto which was grown a confluent monolayer of ovine pulmonary artery endothelial cells. The abluminal chamber filtrate was collected for timed periods during increases in transendothelial pressures of 5, 10, 15, and 20 cmH2O. The transendothelial water flux was linearly related to the hydrostatic pressure. Hydraulic conductivity (Lp) was determined from the slope of this relationship per unit surface area. In the absence of albumin, Lp of the endothelium and the filter was 14.8 +/- 3.8 x 10(-5) cm.s-1.cmH2O-1. The addition of either 2.5 or 5.0 mg/ml ovine serum albumin to the medium reduced Lp values similarly to 2.0 +/- 0.3 x 10(-5) and 2.5 +/- 1.1 x 10(-5) cm.s-1.cmH2O-1, respectively. Removal of albumin from the media reversed the effect of albumin on Lp. The filter Lp value of 3.2 +/- 0.3 x 10(-3) cm.s-1.cmH2O-1 was unaffected by albumin. Endothelial Lp value did not decrease with 5.0 mg/ml of 70-kDa neutral dextran. Albumin decreased Lp in the presence of epsilon-amino-caproic acid to the same extent as albumin alone, suggesting that the positively charged lysine sites on albumin did not mediate the effect. The results indicate that albumin decreases Lp due to an interaction between albumin and the endothelial cell.