Despite the indisputable role of immunoglobulin (Ig)A in the pathogenesis of primary Sjögren syndrome (pSS), the causative abnormality remains largely unknown. As an extension of our report that IgA is oversialylated in this disease, the thrust of the present study was to measure the sialyltransferase (ST) activity in B lymphocytes. ST containing lysates of B cells from 17 pSS patients and 10 controls, were obtained using a combination of detergents, and incubated with affinity purified IgA that had been previously desialylated. The deposition of cytidine 5′ monophosphate sialic acid (SA) by ST from B cells onto IgA was detected by two ELISA based upon the use of biotinylated lectins (Sambucus nigra agglutinin which is specific for α2–6 SA and Maackia amurensis which is specific for α2–3 SA). In parallel, the amount of SA on IgA from ten of the 17 patients and eight of the 10 controls was assayed using the same method. An excess of α2–3 and α2–6 SA on IgA was found in those patients with excessive activity of α2–3 and α2–6 ST. Thus, IgA hypersialylation in pSS patients may result from undue activity of ST.