Sera from systemic lupus erythematosus patients that had antibodies to the ribosomal P proteins were compared in several different assays. The enzyme-linked immunosorbent assay (ELISA) method was compared to the Western immunoblotting method using either affinity purified human or bovine ribosomal P proteins. All 30 normal sera had no significant reactivity with these antigens. The most sensitive test was the ELISA using the human P protein, where 31/32 patients were positive (97%). The assay with bovine proteins in ELISA yielded 28/32 (88%) positive results. Immunoblotting with either bovine or human P protein was equally effective with 30/32 (94%) positive. An ELISA incorporating human P proteins is a more sensitive assay for clinical diagnosis than an ELISA with the bovine protein. Immunoblotting is a sensitive method, but is less convenient and is not quantitative. The ELISA with the human protein appears to be the method of choice.