• Neonatal lupus is a syndrome characterized by cutaneous lupus and/or congenital heart block (CHB). This report reviews our original observations on patients with neonatal lupus during the past five years: (1) Sicca syndrome (SS-A) (Ro) autoantibodies were found in the serum of the mothers and infants, were of maternal origin, and constituted a marker for the syndrome. (2) SS-A autoantibodies were found in the majority of the cases of "idiopathic" CHB and may have been the most common cause of all CHBs. (3) Mothers who had one child affected were at risk for having a second child affected. (4) Mothers were often asymptomatic. (5) HLA associations in this syndrome were HLA-DR3, HLA-B8, HLA-MB2, and HLA-MT2, and these occurred in mothers but not infants. Thus, the HLA association was with autoantibody production rather than tissue injury, a finding that may help clarify genetic and environmental roles in autoantibody-mediated disease.