To investigate patterns of autoreactivity in Sjögren's syndrome, the epitope specificity of anti-La antibodies was determined using recombinant antigens bearing sequences of the amino, middle, and carboxyl portions of the La molecule. Sera from patients with primary as well as secondary Sjögren's syndrome reacted with all three fragments, although the magnitude of the responses varied markedly among individuals. Furthermore, the proportion of antibody binding directed to the different La epitopes showed considerable individual variations, but these patterns were not correlated with specific clinical manifestations. These results suggest that quantitative and qualitative aspects of anti-La responses in Sjögren's syndrome are determined by factors distinct from those determining the clinical expression of disease.