Proteoglycan synthesis of mild-to-moderate osteoarthritic human knee cartilage was compared with that of normal cartilage of the same donor. Immediately after cartilage was obtained, the synthesis rate of proteoglycans was higher for osteoarthritic cartilage than for normal cartilage. Proteoglycan synthesis was then located, for both normal and osteoarthritic cartilage, in the middle and deep zone. However, after 4 days of culture, proteoglycan synthesis rate was higher for normal cartilage than for osteoarthritic cartilage. The reason for this transition from a lower to a higher proteoglycan synthesis rate was a strong increase in the proteoglycan synthesis in the superficial zone of normal cartilage. This was not observed for the osteoarthritic cartilage. The chondrocytes in the superficial zone of osteoarthritic cartilage, in contrast to normal cartilage, were mainly joined in cell clusters and proliferating. This may explain their inability to contribute to proteoglycan synthesis.