Autoantibody, HLA studies and C4 phenotypes were performed on twins discordant for isolated congenital heart block. Serum from the mother and cord blood from the infants revealed Ro(SSA) and La(SSB) antibodies in all three sera. No significant difference in Ro(SSA) antibody titre was noted in the cord blood of either twin when compared with maternal titres, as detected by a sensitive ELISA assay. The infants' mother was HLA-DR3 positive. Both infants had identical HLA and C4 phenotypes. Immunoblot analysis revealed that sera from both mother and infants reacted with the 52-kDa Ro(SSA) macromolecule. Quantitative cord blood IgM levels were not elevated in either twin. This study indicates that placental transfer of anti-Ro(SSA) or anti-La(SSB) alone to the fetus is not sufficient for the expression of congenital complete heart block. We conclude from this experiment of Nature that there must be a second event determining which infant develops complete heart block, but this is unknown at present.