A quantitative immunoassay using a highly purified antigen from HeLa cells has allowed us to detect antibodies to SSB/La in 11/20 patients with primary Sjögren's syndrome (SS), 15/33 with SLE, and 11/35 with progressive systemic sclerosis (PSS). However, positive results were found in only 2/12 patients with idiopathic Raynaud's disease and 2/20 with rheumatoid arthritis, including 4 with secondary SS. Anti-SSB/La were associated with extraglandular manifestations in primary SS, and with a diffuse sclerodermic pattern in PSS. In SS, SLE and PSS, a positive anti-SSB/La test was strongly associated with nodal or spleen enlargement and with an increased level of gamma-globulins. A direct association was also found with positive tests for rheumatoid factors, anti-SSA/Ro and anti-Scl 70. An inverse relationship was however found with anti-nRNP +/- Sm and anticentromere antibodies. Our data suggest that anti-SSB/La antibodies can be regarded as a marker of B-lymphocyte activation in patients with either primary SS, SLE or PSS.