Albumin reduces capillary hydraulic conductance (Lp) even at low concentrations. To determine if part of this barrier protective effect might be extracellular, we studied the effects of bovine serum albumin (BSA) on Lp of self-assembled basement membrane (Matrigel). Lp with tris(hydroxymethyl)aminomethane (Tris) buffer superfusate was stable at 1.77 +/- 0.22 x 10(-5) (SE) cm.s-1.cmH2O-1 over several hours. At 0.1 g/dl BSA, experimental/control (Tris) Lp fell to 83.1 +/- 6.0% (2P < 0.025), with decreases to 72.4 +/- 3.7% at 1 g/dl (2P < 0.005), 45.3 +/- 5.1% at 2.5 g/dl (2P < 0.001), and 45.0 +/- 4.8% at 4.0 g/dl (2P < 0.001). In separate experiments, BSA arginine groups were neutralized by 1,2-cyclohexanedione (CHD), and experimental/control Lp values were measured. At 2.5 g/dl, CHD-BSA depressed Lp to 54.4 +/- 4.8%, while unmodified BSA reduced Lp to 40.8 +/- 3.5% of Tris control (2P = 0.05). Finally, soluble arginine at three- and sixfold the arginine in BSA was added to BSA superfusate. For threefold, Lp rose to 120 +/- 8% of BSA level and for sixfold to 129 +/- 9% (2P < 0.05). We conclude that some part of the albumin protective effect is very likely due to consequences on extracellular matrix and that at least 18-22% of this effect is related to arginine groups on albumin when computed from Lp, and up to 34% when viscosity is taken into account. Membrane-saturable arginine-binding sites can be unbound with arginine, thus nullifying part of the barrier protective effect of BSA.