The relation between congenital heart block and maternal connective-tissue disease was studied by antibody screening of serum samples obtained in connection with 45 cases of isolated congenital complete heart block. Serum was available from 41 mothers (17 who had connective-tissue disease and 24 who were healthy) and 21 children. Thirty-four mothers had antibody to a soluble tissue ribonucleoprotein antigen called Ro(SS-A), which was identified by immunodiffusion. Anti-Ro(SS-A) was found in seven of eight serum samples collected from affected children when they were less than three months old but in none of 13 samples obtained when these children were older. It appears that maternal anti-Ro(SS-A) antibody crosses the placenta and is a marker for risk of congenital complete heart block; its absence from maternal serum suggests that a child is unlikely to be affected. Anti-Ro(SS-A) or a related antibody is probably involved in the pathogenesis of congenital complete heart block.