Congenital complete heart block is closely associated with the presence of anti-Ro (SS-A) autoantibodies. Quantitative solid-phase assays for Ro (SS-A) autoantigen and autoantibody have established the presence of Ro (SS-A) in cardiac tissues and have been used to evaluate an informative pedigree. The propositus we describe here had complete congenital heart block and showed anti–Ro (SS-A) binding of 13-fold less than his normal HLA-identical twin sister. Both had identical titers of antinuclear antibody. These data support the hypothesis that anti–Ro (SS-A) may be directly involved in the pathogenesis of congenital complete heart block.