For a better understanding of the part played by the aging of cartilage in the pathogenesis of osteoarthrosis, we attempted to detect functional age-related changes in the knee-joint cartilage of C57B1 mice using histochemical methods and to correlate these changes with the concomitant histological changes. A comparison of 57- and 97-week-old mice revealed a statistically significant age-related focal loss of activity for a number of oxidative enzymes of the chondrocytes. There was an associated significant increase in regressive changes of the chondrocytes. A relation probably exists between these two changes, inasmuch as the focal loss of enzyme activity precedes and possibly gives rise to the regressive changes. A comparison with the changes described in the articular cartilage of other species including man suggests that the phenomena observed are inherent age-related changes. The loss of activity of all the enzymes investigated indicates a far-reaching derangement of cellular metabolism, leading to impaired synthesis of proteoglycans. Since these compounds are major determinants of the physical properties of articular cartilage, the changes described might render the cartilage more vulnerable and might thus play a major part in the pathogenesis of osteoarthrosis.