Compared with normal cartilage, the water content, extraction yields, and capacity of 34SO4 incorporation, were found to be increased in articular cartilage from rheumatoid joints, which also synthesizes an increased proportion of low and middle density small size proteoglycans (PGs), enriched in dermatan sulfate. These small [35S]-PGs also possess longer glycosaminoglycan side chains and lack the ability to interact with hyaluronan. An altered pattern of PG synthesis of rheumatoid chondrocytes may contribute to cartilage damage in this condition.