Precipitating antibody to an antigen present in cytoplasm was detected in the sera of 7 patients with systemic lupus erythematosus, 1 patient with an overlap toid arthritis, and 1 patient with mixed connective tissue disease. By physicochemical and enzymatic studies, the antigen was shown to have the properties of ribosomal ribonucleoprotein (gamma-RNP). Cytoplasmic staining in immunofluorescence was observed with all the 9 sera containing antibodies to gamma-RNP. In certain cases, cytoplasmic staining was associated with nucleolar staining. Antibody to gamma-RNP is different in immunologic specificity and clinical significance from antibody to nuclear RNP and is present primarily in patients with systemic lupus erythematosus.