In this study of 71 children with systemic lupus erythematosus (SLE) and 188 of their first-degree relatives, we demonstrated that the development of SLE in male children younger than age 18, and in all children younger than age 10 at the time of diagnosis, is strongly correlated with the presence of antibodies to Ro (SS-A) in the mother's serum. When the relative antibody concentration was quantified, increased quantities of antibody to Ro (SS-A) were also found in mothers of male probands and mothers of probands whose SLE was diagnosed before age 10. No similar association was found for the presence or amount of antibody to Ro (SS-A) in other first-degree relatives or for antibody to La (SS-B) or nuclear RNP in any relative. The explanation for the association of maternal anti-Ro (SS-A) antibodies and early diagnosis of SLE or male sex is not apparent. These findings extend the association of maternal antibodies to Ro (SS-A) from transient "neonatal" SLE to SLE in childhood, and suggest that maternal antibodies to Ro (SS-A) may be of fundamental importance in the pathogenesis of some cases of childhood SLE.