Serum C3, C4 and total hemolytic complement (CH50) levels were measured for 21 children with systemic lupus erythematosus (SLE) and 81 first degree relatives. The mean serum C4 and CH50 levels of the 12 relatives with antinuclear antibodies (ANA( were depressed to levels equal to those of the index cases. A similar depression was not found for C3, nor was there a depression of C3, C4, or CH50 in the relatives without ANA. If preexistent depression of C4 levels can be documented in the ANA-positive relatives of index cases, it may provide an explanation for the inherited predisposition to SLE in some families.