Serum cytidine deaminase (CD) as a marker of disease activity was assessed in 100 patients with rheumatoid arthritis (RA) and in 102 assessments of 85 patients with systemic lupus erythematosus (SLE). In RA CD levels correlated well with clinical assessment of disease activity, but were not influenced by varying dosages of ibuprofen as therapy. In SLE significant correlations were found between CD and anti-DNA antibody titers, as well as C3 complement levels. A subset of clinically active patients with SLE with elevated CD levels but normal anti-DNA titers was identified. Serum CD levels may be a clinically useful marker in RA and in certain subgroups of patients with SLE.