The demonstration that free DNA binds to collagen suggests that the local formation of collagen bound DNA-anti-DNA complexes might be important in the pathogenesis of some autoimmune disorders. We explored the interaction of single and double-stranded DNA (ssDNA and dsDNA) with native type II collagen. Each of 6 sera, known to contain antibodies to dsDNA and ssDNA, was employed in an enzyme linked immunosorbent assay as an antibody reagent for the detection of collagen bound DNA. Six sera without such antibodies served as controls. Our results indicate that significant binding of ssDNA (t = 3.22; p less than .005) and dsDNA (t = 3.06; p less than .01) to type II collagen occurs.