Pyridinoline (Pyr) and deoxypyridinoline (Dpyr) are new markers of type I and II collagen degradation. Dpyr is a specific marker of type I collagen resorption in bone, whereas Pyr is released from type I and II collagen in bone and cartilage. We assessed the effect of six repeated iv methylprednisolone (MP) pulses or placebo at 4 week intervals in combination with DMARDs, on the excretion of Pyr and Dpyr in 86 patients with active RA. Pyr and Dpyr correlated significantly with clinical and biochemical markers of disease activity. After an initial decrease in Pyr on day 7 in the MP treated group, Pyr was significantly increased in both treatment groups at day 28. Dpyr remained unchanged after a single MP pulse in contrast to significant increases after 7 and 28 days in the placebo group. Pyr and Dpyr were significantly decreased after 24 and 52 weeks in the MP group, whereas no changes were observed in the placebo group. Pyr and Dpyr correlate with clinical and biochemical markers of disease activity in patients with active RA. Repeated MP pulses in combination with DMARDs in RA, do not seem to have a deleterious effect on bone resorption measured by Dpyr excretion, on the contrary MP pulses may even prevent an increase in bone resorption, as indicated by the decreased Dpyr observed in this group.