Clinical, serologic, and genetic findings in Sjögren's syndrome patients were correlated with quantitative determinations for antibody against Ro (SS-A), La (SS-B), and nRNP (Sm) using newly developed, sensitive solid-phase assays. In 86 Sjögren's syndrome patient sera, more than 96% had anti-Ro (SS-A), and 87% had anti-La (SS-B), spanning a 4.8 log10 range of autoantibody concentration, whereas only 95% of the patients had anti-nRNP (Sm). Low levels of anti-Ro (SS-A) and anti-La (SS-B) were found in 10% and 12.5%, respectively, of the 40 normal control sera. In Sjögren's syndrome patients, the level of anti-Ro (SS-A) correlated strongly with that of anti-La (SS-B) (r = 0.80; P less than 0.0001) but not with the level of anti-nRNP (Sm). We found much higher levels of anti-Ro (SS-A) and anti-La (SS-B) in patients with purpura, leukopenia, lymphopenia, and increased polyclonal gamma globulins than in those without these conditions (between 4.3-fold and 17-fold higher; P less than 0.001 to P less than 0.05). Anti-Ro (SS-A) and anti-La (SS-B) levels correlated with the rheumatoid factor titer and with the concentrations of total globulin, IgG, and IgA, but not with the IgM concentration. The association of rheumatoid factor titer with levels of anti-Ro (SS-A) and anti-La (SS-B) occurred only in patients with primary Sjögren's syndrome. Antinuclear antibody titers correlated with levels of anti-Ro (SS-A) and anti-nRNP (Sm). HLA-DR3-positive patients had higher levels of anti-Ro (SS-A) and anti-La (SS-B).