Cells spontaneously secreting IgG or IgM antibodies to DNA or to common environmental antigens—influenza virus haemagglutinin, adenovirus hexon and mannan from Candida albicans—have been enumerated by ELISA spot in blood from patients with systemic lupus erythematosus (SLE) and normal donors. Mean values were raised for all antigens in the disease, with those for DNA being no greater than for the other antigens. In normal donors, levels of IgM-secreting cells were similar for DNA and the environmental antigens whereas virtually no IgG anti-DNA secreting cells were found. When results were expressed relative to total numbers of IgG or IgM-secreting cells, the differences between the groups disappeared or were greatly reduced in all systems except IgG anti-DNA. These findings are consistent with a requirement for both polyclonal activation and a self-antigen response in the production of IgG autoantibodies in SLE.