To determine the prevalence of anticardiolipin antibodies (aCL) in pediatric systemic lupus erythematosus (SLE) and their possible association with clinical manifestations, aCL were measured in sera of 32 patients with the onset of SLE before age 16. IgM and IgG aCL were determined by ELISA and values compared to those of 12 patients with juvenile rheumatoid arthritis (JRA), 15 age matched asthmatics, and 32 adult controls. aCL were demonstrated in sera of 16 of 32 (50%) children with SLE, 5 of 12 (42%) patients with JRA, 1 of 15 (7%) asthmatics, and in none of the 32 adult controls. Serial samples on 11 patients with SLE showed fluctuations in aCL levels that often corresponded to disease activity; the highest levels occurred in patients during periods of seizure activity and other neurologic events. The antibodies were not crossreactive anti-DNA antibodies as shown by the failure of DNA to inhibit binding to cardiolipin. These data suggest that the prevalence of aCL is similar in pediatric and adult SLE and that aCL levels may vary with disease activity, especially neurologic disease.