The effect of strenuous joint loading on the metabolism of articular cartilage in man is not known. The development of a non-invasive immunoassay for the assessment of the catabolism of cartilage aggrecan has enabled us to quantify keratan sulfate (KS), a component of aggrecan, in the serum of fifteen male marathon runners. Serum KS was measured by an ELISA before and immediately after a marathon (42 km), as well as 48 hours after the completion of the race. The mean level at rest was similar to those previously reported for another population of age-matched males. There was no statistically significant difference in the serum level of KS at the three different readings. Further, there was no correlation between age, height, weight and performance time, and the serum level of KS at any of the three different times. We conclude that marathon running by carefully trained runners causes neither a transient nor a sustained increase in proteoglycan catabolism in articular cartilage.