The material properties of normal cadaveric human cartilage in the ankle mortice (tibiotalar articulation) were evaluated to determine a possible etiologic mechanism of cartilage injury of the ankle when an obvious traumatic episode is not present. Using an automated indentation apparatus and the biphasic creep indentation methodology, creep indentation experiments were performed in five sites in the distal tibia, one site in the distal fibula, and eight sites in the proximal talus of 14 human ankles (seven pairs). Results showed significant differences in the mechanical properties of specific human ankle cartilage regions. Topographically, tibial cartilage is stiffer (1. 19 MPa) than talar cartilage (1.06 MPa). Cartilage in the anterior medial portion of the tibia has the largest aggregate modulus (H A =1.34 MPa), whereas the softest tissue was found to be in the posterior lateral (0.92 MPa) and the posterior medial (0.92 MPa) regions of the talus. The posterior lateral ridge of the talus was the thickest (1.45 mm) and the distal fibula was the thinnest (0.95 mm) articular cartilage. The largest Poisson's ratio was found in the distal fibula (0.08). The lowest and highest permeability were found in the anterior lateral regions of the astragalus (0.80 × 10⁻¹⁵ m⁴N⁻¹sec⁻¹) and the posterior medial region of the tibia (1.79 × 10⁻¹⁵ m⁴N⁻¹sec⁻¹), respectively. The anterior and posterior regions of the lateral and medial sites of the tibia were found to be 18–37% stiffer than the anatomically corresponding sites in the talus. The biomechanical results may explain clinically observed talar dome osteochondral lesions when no obvious traumatic event is present. Cartilage lesions in a repetitive overuse process in the ankle joint may be related to a disparity of mechanical properties between the articulating surfaces of the tibial and talar regions.