Neonatal lupus erythematosus (LE) is a syndrome that is manifested by LE skin lesions and/or congenital heart block, occurring in infants at, or shortly after, birth. The syndrome is believed to be caused by transplacental passage of an IgG antibody, usually the anti-Ro (SS-A) antibody, from the mother to the infant. Although the mother may have a connective tissue disease or may be healthy, the common characteristic is the presence of maternal circulating anti-Ro antibody. It has been believed that the HLA determinants demonstrated in children who have neonatal LE were not a factor in the expression of the syndrome. We report the occurrence of neonatal LE, manifested by photosensitivity and discoid LE skin lesions, in one fraternal twin. HLA studies of this affected twin demonstrated the presence of DR3. Anti-Ro antibody was present in the mother, but was not present in either child at 4 months post-delivery. HLA determinants may be involved in the expression of disease in neonates who have been exposed to the anti-Ro antibody. Furthermore, the presence of circulating antibodies in the unaffected twin causes us to question the assumption that the anti-Ro antibody is the causative factor for the occurrence of tissue injury in children with neonatal LE.