We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (R-q), average collagen content (A(1)) and collagen orientation (A(12)) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (Rc) had a significant coefficient of determination with R-q and A(12) (R-LMMm(2) = 0.79); however, R-c did not correlate with A(1). Concerning the collagen characteristic in the superficial zone, Rc was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. (C) 2017 World Federation for Ultrasound in Medicine & Biology.