We evaluated the microscale frictional response of human articular cartilage in different osteoarthritis stages using an atomic force microscope. Four human femoral heads (60-80 years old) with different osteoarthritis stages were explanted, and two cylindrical cartilage samples were sectioned from each femoral head. The microscale frictional coefficient mu of human cartilage in phosphate-buffered saline increased with increasing osteoarthritis stages, resulting in mu = 0.119 +/- 0.036 for stage 0 (normal cartilage), 0.151 +/- 0.039 for stage I, 0.158 +/- 0.041 for stage 2, and 0.409 +/- 0.119 for stage 3. Statistically significant differences of mu values for different osteoarthritis stages were detected only between stage 3 and other stages (p < 0.0001). The average surface roughness Rq significantly increased with increasing osteoarthritis stages, ranging from 137 +/- 25 nm for stage 0 to 533 +/- 196 nm for stage 3. A significant correlation between mu and Rq for different osteoarthritis stages was observed (R2 = 0.981). These results demonstrate a positive correlation between the osteoarthritis stages and cartilage surface roughness, and the dependence of the human cartilage frictional response, on osteoarthritis progression. The results could be due to a decrease in the superficial zone protein concentration during the natural progression of osteoarthritis.