Antibodies to Ro(SS-A) are an important laboratory parameter of congenital heart block (CHB), but the maternal presence of anti-Ro(SS-A) antibodies does not always lead to this fetal acquired autoimmune disease. The current study investigated quantitative and qualitative differences of anti-52, -60 kD Ro(SS-A), 0La(SS-B) and -U1RNP(-C, -A, -68 kD) autoantibodies (either IgG or IgM) in sera derived from 16 infants with CHB and their mothers compared to eight healthy anti-Ro(SS-A) positive infants (controls) born to SLE mothers. No serum sample contained IgM auto-antibodies of the specificities investigated. Anti-60, 52 kD Ro(SS-A) and La(SS-B) IgG antibodies coincided in 9/16 CHB cases, exclusively (P < 0.05). Associated anti-52 kD Ro(SS-A) and -La(SS-B) IgG antibodies were detected in 14/16 CHB and in 3/8 control cases (P < 0.05). Anti-U1RNP 68 kD antibodies occurred in 1/16 CHB infants and in 4/8 controls. In general, newborn and maternal antibody patterns and reactivities were similar in all cases investigated. The fetal CHB sera contained significantly higher IgG levels of anti-52 kD Ro(SS-A) (P < 0.005) and -La(S-B) (P < 0.015) compared to control samples. Sera from mothers with CHB children had significantly higher levels of anti-52 kD Ro(SS-A) (P < 0.015) and -La(SS-B) (P < 0.015) IgG antibodies than those of the control group. Thus, the coincidence of anti-52 kD, -60 kD Ro(SS-A) and -La(SS-B) IgG antibodies as well as significantly increased levels of antibodies to 52 kD Ro(SS-A) and La(SS-B) are associated with evidence of complete congenital heart block. The data suggest that the known associated humoral autoimmune findings are exclusively of maternal origin.