To characterize patterns of autoantibody expression in pediatric and adult systemic lupus erythematosus (SLE), IgG and IgM antibodies to cardiolipin (aCL) and single-stranded DNA (anti-DNA) were measured in sera from 32 pediatric and 36 adult patients. Antibody levels were assessed by isotype-specific ELISA and compared with 15 pediatric disease controls and 36 healthy adult controls. These determinations revealed significant differences in the pattern of IgG and IgM autoantibody expression in adult and pediatric patients. IgM aCL were more common in the pediatric than adult SLE population with 11 of 32 pediatric patients being positive compared to only 4 of 36 in the adult group (p less than 0.05). Conversely, enhanced IgG autoantibody production was observed in the adult group as 27 of 36 adult patients were positive for IgG anti-DNA compared to only 16 of 32 children (p less than 0.05). Analysis of sequential sera showed differences in the temporal expression of IgG and IgM autoantibodies as well as variability between anti-DNA and aCL responses over time. Our data suggest differences in the isotype profile of autoantibody responses in pediatric and adult SLE and provide further evidence for heterogeneity in the mechanisms of autoantibody production.