DNA levels were measured in synovial fluids and sera of 106 patients with rheumatoid arthritis (RA), osteoarthritis (OA), gout, pseudogout, and posttraumatic arthritis (TRA). In synovial fluids, the highest concentration was found in rheumatoid arthritis (mean +/- SE 18 +/- 3 microgram/ml for seropositive and 9 +/- 1 microgram/ml for seronegative variants), gout and pseudogout (17 +/- 3 microgram/ml). In contrast, the levels in patients with OA or acute TRA were very low: 0.8 +/- 0.1 microgram/ml an 1.1 +/- 0.2 microgram/ml, respectively. The differences between the means of the first disease group and OA or TRA is statistically significant. A similar pattern was observed for DNA levels in the circulation: in rheumatoid arthritis, the mean concentration was 135 +/- 28 ng/ml and 164 +/- 39 ng/ml for seropositive and seronegative RA, respectively. Again the levels in OA and TRA were much lower, 52 +/- 18 ng/ml and 0 ng/Ml, respectively. The latter are not significantly different from the mean levels of 95 normal, healthy controls (14 +/- 3 ng/ml), whereas the concentration of DNA in the serum of RA patients is significantly higher than in OA, TRA, or normal controls. Serial determinations of DNA and other criteria of disease activity (leukocytes and protein levels in synovial fluid, blood sedimentation rate) in individual patients revealed a strong correlation of elevated values with active episodes. THe results suggest that these parameters reflect tissue damage.