Primary Sjögren's syndrome (SS) is an autoimmune rheumatic disease characterized by T cell hypoactivity. To understand the diminished T cell response to activation signals, we measured nucleoprotein DNA-binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay. Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an october sequence (Oct-1). This Oct-1-binding phenotype remained stable in culture for up to 3 days prior to activation. This abnormality was not seen in resting T cells nor T cells from patients with systemic lupus erythematosus, rheumatoid arthritis (RA), or SS accompanied by RA. The SS Oct-1 DNA-binding abnormality correlated significantly with an inability of cells to exit the Gzero/G1 cell cycle phase when stimulated in vitro. Importantly, nucleoprotein extracts showing decreased DNA-binding activity had normal amounts of Oct-1 proteins as determined by immunoprecipitation, implying a functional defect in the Oct-1 protein. Moreover, defective DNA binding was corrected by treatment with acid phosphatase.