The restrictive properties of liver blood-lymph barrier to endogenous plasma protein fractions of varying molecular size were studied at different hepatic venous pressures (and lymph flows) using steadystate lymph to plasma protein concentration ratios. At control hepatic venous pressures (0-2 mmHg) the lymph to plasma concentration ratios of the various protein fractions indicate significant selectivity by the liver blood-lymph barrier to macromolecules on the basis of molecular size. The sieving observed was consistent with equivalent pore radii of 180-250 Å. The transsinusoidal oncotic pressure gradient ranged between 4.0 and 8.0 mmHg at control venous pressures. As venous pressure was increased, liver lymph flow and lymph to plasma protein concentration ratio increased while the blood-lymph oncotic pressure gradient decreased. Liver lymph flow was linearly related to hepatic venous pressure. At lymph flows ≥10 × control, there is no longer a sieving effect on plasma protein; findings consistent with pore radii in excess of 1000 Å. The results of this study suggest that maximal sieving by the liver blood-lymph barrier occur at normal capillary filtration rates and support the possibility that the interstitium is the rate limiting barrier for blood to lymph transport of macromolecules in the liver.