Cryoprecipitates from systemic lupus erythematosus (SLE) patients with high levels of anti DNA antibodies show a sharply migrating large circuIating DNA species of about 17-20 kb (M. Rieber et al., Clin. exp. Immunol. (1986) 66, 61). We have now used Southern blot analysis of circulating DNA from different individuals to analyse the relative cross-hybridization of circulating DNA from different individuals, as well as their homology with genomic DNA from different species. Molecular hybridization showed significant homology of the various circulating DNA examined, only with human genomic DNA, but limited cross -reactivity among circulating DNA from different individuals. This suggest s that the circulating DNA is composed of sequences repeated in hum an genomic.DNA and by specific sequences unique to circulating DNA from some individuals. Our data suggests the possibility of using probes derived from the specific sequences now reported in the circulating DNA, in gene typing and m the analysis of susceptibility to disease.