We previously reported that levels of D-dimer, a measure of fibrin degradation, were elevated in patients with active s-JRA. We therefore analyzed serial levels in 11 patients to determine whether such levels might parallel disease course or predict outcome. Levels were measured by a semiquantitative latex agglutination assay and were reported as <0.5, 0.5-2, 2-8, or >8 ng/dl (scored as 0, 1, 2, 3 respectively). We obtained 3-10 of these levels per patient over 5-34 months, and correlated them with hematocrit, WBC and platelet counts, ESR, joint count, duration of AM stiffness, and maximal fever. In this group of patients, a D-dimer score of 2 or 3 indicated (1) a current severe complication (pericarditis, disseminated intravascular coagulopathy), (2) subsequent severe course defined as ≥4 months of persistent fever of ≥38.3° C, or severe arthritis (joint count >10 or AM stiffness≥45 min), or (3) recurrence of any of these signs/symptoms upon tapering of corticosteroids (steroid dependence). A score of ≥1 in patients on any dose of corticosteroid or other immunomodulatory agent (methotrexate, azathioprine, immunoglobulin) predicted disease exacerbation with medication taper, even when other markers such as hematocrit, platelet count, and ESR had normalized. Conversely, a score of 0 in patients off these agents or on low-dose steroid (≤0.25 mg/kg/d) predicted remission or mild course during the remainder of the follow-up period, even when other markers such as ESR were still abnormal. These data indicate that levels of D-dimer may predict response to medications and short-term outcome in s-JRA.