Sixteen patients with primary Sjogren's syndrome, verified according to the Copenhagen criteria, were investigated for evidence of complement activation. Thirteen of the patients had intact functional activity of both the classical and alternative pathways, with normal concentrations of the complement proteins Clq, Cls, C3, C4 and the complement protein fragments C2a and C3d in the circulation. In contrast, three patients showed clear evidence of complement activation. Further investigation of these patients revealed manifestations of glomerulonephritis, vasculitis and primary biliary cirrhosis. Six months later, one patient developed a malignant non-Hodgkin lymphoma.We conclude that complement activation is generally not associated with primary Sjögren's syndrome. Evidence of complement activation in patients considered to have primary Sjögren's syndrome should raise the suspicion of concomitant systemic disease and/or extraglandular activity.