In order to determine whether circulating antigen-antibody complexes in systemic lupus erythematosus (SLE) consist of DNA and anti-DNA, cryoglobulins were isolated from the sera of 38 patients with SLE nephritis and analysed for DNA and anti-DNA. Cryoglobulins were detected in 36 of the 38 sera, and DNA was found in 30 of 33 examined by either fluorescence of ethidium bromide or a radioimmunoassay. Anti-DNA activity was not detectable in any of the whole cryoglobulins but anti-IgG activity was found in 17. Twenty cryoglobulins were therefore treated by acid dissociation and ultracentrifugation to obtain isolated immunoglobulins; IgG was isolated from all, and IgM from eight. Using a modified Farr assay to detect anti-dsDNA and an enzyme-linked immunoadsorption assay to detect anti-ssDNA, anti-dsDNA activity alone was found in five IgG fractions, anti-ssDNA activity alone in five, and both anti-ds- and anti-ssDNA activity in four. Anti-dsDNA activity was found in three of the IgM fractions. In all, anti-dsDNA activity was found in nine of these 20 cryoglobulins, and anti-DNA in 14. Analysis of these 14 cryoglobulins with anti-DNA Ig fractions showed that there was enrichment of the IgG anti-DNA activity in the cryoglobulin compared to the patient's serum in all but two cases. In six of the 20 cryoglobulins studied there was no detectable anti-DNA activity in isolated IgG or IgM fractions. We therefore concluded that DNA-anti-DNA complexes were present in most of our patients with SLE nephritis, but there was clearly a substantial minority in whom they were undetectable. In some of the latter who also had active disease the cryoglobulins had anti-IgG activity. Thus it would seem that SLE can occur in the absence of DNA-anti-DNA complexes, but with other complexes present. DNA was also found in cryoglobulins isolated from patients with idiopathic glomerulonephritis, but, in contrast to recent reports, anti-DNA activity was not detectable in immunoglobulins isolated from their cryoglobulins.