IgG was purified from 91 serum samples obtained from patients with systemic rheumatic diseases and examined for the presence of antinuclear antibodies reactive with small ribonucleoprotein (RNP) complexes. Antibody specificity was determined by autoradiographic detection of 32P labeled RNA which had been separated by polyacrylamide gel electrophoresis. This RNA was extracted from immune complexes formed by adding purified IgG to a homogenate of 32P labeled HeLa cells. Anti-RNP antibodies were detected in 70% of these samples. Specific antibodies detected were anti-(U1)-RNP (35%), anti-Sm (30%), anti-Ro (24%), and anti-La (10%). Other antibodies (9%) were reactive with structures containing 5S and 5.8S RNA or 4S RNA. There was a significant relationship between the presence of anti-RNP antibodies in patients with systemic lupus erythematosus (SLE) (78%) as opposed to their presence in patients with non-SLE rheumatic disorders (45%). However, taken individually, anti-Ro was the only antibody whose presence in SLE patients (30%) was significantly greater than its presence in non-SLE patients (5%). Vasculitis was the only clinical manifestation found to correlate with the presence of a particular antibody, anti-(U1)RNP. There is some suggestion of a racial distribution of antibody types.