The urinary concentrations relative to creatinine of the collagen crosslinks, pyridinoline (PYD) and an analogue derived specifically from bone collagen, deoxy-pyridinoline (DPD), were measured using a high performance liquid chromatography (HPLC) technique in 41 patients with rheumatoid arthritis (RA) and 45 patients with osteoarthritis (OA), and were compared with values of 118 healthy control individuals. The levels of DPD were increased significantly in both RA and OA suggesting accelerated bone degradation in both disease groups. PYD concentrations were also significantly increased in both diseases, but larger increases were detected in patients with RA, for which this index correlated with clinical measures of joint involvement and biochemical variables of inflammatory activity. Cross-sectional studies showed that treatment with disease modifying drugs (gold and D-penicillamine) led to decreased crosslink levels but longterm corticosteroids resulted in increased urinary crosslinks, probably due to the induction of bone resorption. Measurement of both pyridinium crosslinks in urine may therefore provide information on the stage, activity, level of bone involvement and efficacy of drug therapy in arthritic diseases.