Site-specific anti-RNA antibodies were sought in 120 sera of patients with autoimmune diseases by ribonuclease-protection assay using six fragments covering 28S ribosomal RNA (rRNA) as antigens. Fifteen of 90 sera from patients with systemic lupus erythematosus (SLE), but none of 30 sera of the other autoimmune diseases, provided a 60 nucleotide fragment within a region termed the 'GTPase domain' of 28S rRNA. These sera had potency to precipitate 0.42-69.3 nmol of the RNA domain per ml serum, which was higher than 15 control sera of healthy donors. No other specific antigenic site was detected in 28S rRNA under conditions used. All of the 15 sera having this anti-RNA antibody showed reactivity to ribosomal P proteins (anti-P), and two of them contained an additional antibody to ribosomal protein L12. These results suggested a strong association of the production of these three antibodies. Since P and L12 proteins form a stable complex with the GTPase domain, this serological association may result from an immune response to epitopes clustered on a single RNA-protein complex domain in ribosomes.