This study quantified the apparent and intrinsic hydraulic permeability of human medial collateral ligament (MCL) under direct permeation transverse to the collagen fiber direction. A custom permeation device was built to apply flow across cylindrical samples of ligament while monitoring the resulting pressure gradient. MCLs from 5 unpaired human knees were used (donor age 55 AE 16 yr; 4 males, 1 female). Permeability measurements were performed at 3 levels of compressive pre-strain (10%, 20% and 30%) and 5 pressures (0.17, 0.34, 1.03, 1.72 and 2.76 MPa). Apparent permeability was determined from Darcy's law, while intrinsic permeability was determined from the zero-pressure crossing of the pressure-permeability curves at each compressive pre-strain. Resulting data were fit to a finite deformation constitutive law [Journal of Biomechanics 23 (1990) 1145-1156. The apparent permeability of human MCL ranged from 0:40 AE 0:05 to 8:60 AE 0:77 Â 10 À16 m 4 =N s depending on pre-strain and pressure gradient. There was a significant decrease in apparent permeability with increasing compressive pre-strain ðp ¼ 0:024Þ and pressure gradient ðpo0:001Þ; and there was a significant interaction between the effects of compressive pre-strain and pressure ðpo0:001Þ: Intrinsic permeability was 14:14 AE 0:74; 6:30 AE 2:13 and 4:29 AE 1:71 Â 10 À16 m 4 =N s for compressive pre-strains of 10%, 20% and 30%, respectively. The intrinsic permeability showed a faster decrease with increasing compressive pre-strain than that of bovine articular cartilage. These data provide a baseline for investigating the effects of disease and chemical modification on the permeability of ligament and the data should also be useful for modeling the poroelastic material behavior of ligaments. r