BACKGROUND Neonatal lupus erythematosus (NLE) is a distinct subset of lupus characterized by cutaneous findings (50%), cardiac conduction defects (50%), and autoantibodies to Ro (SS-A) antigen. HLA typing studies of Ro (SS-A) antibody-positive mothers of infants with NLE have shown an association with the HLA-DR3 phenotype. We report the clinical and serologic features of two infant-mother pairs who are U1RNP antibody positive and Ro (SS-A) antibody negative. HLA typing is reported on these infants, their mothers, and two additional infant-mother pairs with U1RNP antibody-positive lupus whose clinical features have been reported previously. METHODS Cutaneous findings included malar erythema, annular and polycyclic plaques, and scales that resolved with residual telangiectasia and hyperpigmentation 6 months after birth. Systemic abnormalities, including complete heart block, were absent. HLA typing revealed HLA-DR3 in two of four mothers, HLA-DR4 and HLA-DRw53 in two of four mothers, and either HLA-DQ1 or HLA-DQ3 in four of four mothers. No distinct HLA associations were seen in the three infants examined. CONCLUSIONS The spectrum of cutaneous disease in U1RNP antibody-positive infants is similar to Ro (SS-A) antibody-positive infants with NLE. Complete heart block was not a feature of U1RNP antibody-positive NLE. HLA typing studies show a more diverse immunogenetic pattern in U1RNP antibody-positive mothers of infants with NLE compared with Ro (SS-A) antibody-positive mothers.