We examined the ability of the mononuclear phagocyte in vitro to degrade 45Ca-labeled bone particles to determine whether this assay allowed us to monitor disease activity in patients with juvenile rheumatoid arthritis. The monocytes from patients with juvenile rheumatoid arthritis receiving no anti-erosive therapy (n = 10) degraded significantly more bone than did cells obtained from normal controls (n = 10, P less than 0.001) or patients with juvenile rheumatoid arthritis receiving either gold thioglucose (n = 4, P less than 0.001) or D-penicillamine (n = 6, P less than 0.005). In two patients monitored for either 8 or 11 months, results of monocyte assays were found to parallel the clinical course. We conclude that in vitro monocyte bone degradation assays may provide a means of assessing joint activity in patients with juvenile rheumatoid arthritis. Further, this study and others indicate that mononuclear phagocytes are capable of causing erosive changes.