Infants with neonatal lupus erythematosus have congenital heart block, transient cutaneous lesions, or both. Mothers of these infants have SSA/Ro autoantibodies that are passed across the placenta to the fetus and that have been temporarily associated with the syndrome. Six families with neonatal lupus were studied by HLA typing. All seven infants had transient cutaneous lesions, congenital heart block, or both. Five of six mothers were asymptomatic and one had Sjögren's syndrome. Six of seven infants and all six mothers had antibodies to SSA/Ro in their sera. The infants became seronegative by age 8 months. Five mothers were positive for HLA-DR3, five for HLA-MB2, six for HLA-MT2, and six for HLA-B8. No HLA associations were seen in infants. Gene products of the DR or similar regions may be associated with autoantibody production but not with other events in tissue injury.