The levels of serum keratan sulfate (KS) were measured in 9 dogs who underwent anterior cruciate ligament transection. They rose in some animals as early as 7 days after surgery, long before any decrease in the articular cartilage content of KS containing proteoglycans could be measured; and they reached their maximum in most dogs by Day 21 and remained elevated for at least 13 weeks. In contrast, the serum levels of the KS epitope showed no increase in sham operated control animals. Analysis of synovial fluid suggested an increase in the catabolism of cartilage proteoglycans in the operated joint contributed significantly to the increased levels of serum KS.