The specificity of antibodies directed against dsDNA for SLE in a childhood population was tested by analyzing sera from 62 children with lupus and 283 children with other known or suspected autoimmune diseases. The role of these antibodies in the manifestations of SLE was then examined by correlating dsDNA Ab titer with clinical manifestations in 311 sera from 20 children followed for a mean of 51 months. Antibodies to dsDNA were found to be highly specific for SLE. The presence of antibodies in titers of 1:80 or greater correlated with the presence of active disease, arthritis, and rash, but not with azotemia, proteinuria, or increasing proteinuria; this indicated that their role in the induction of lupus nephritis was different from that in the induction of rash and arthritis. This may be due to a requirement for small immune complex formation during times of antigen excess in the initiation of lupus nephritis.