Sera from 298 patients with sicca syndrome and connective tissue diseases were examined for the presence of anti SS-A, SS-B and RNP antibodies using double diffusion techniques, and the clinical implication of these antibodies was studied. Among the 298 patients, 147 had sujective symptoms of dry eye and/or dry mouth, and abnormal lacrimal and/or salivary glands (clinical Sjogren's syndrome). The other 51 patients lacked subjective symptoms, but had histologically abnormal salivary glands (subclinical Sjogren's syndrome). Anti SS-A antibody was present in high incidence both in the patients with sicca syndrome and in those with Sjogren's syndrome associated with connective tissue diseases. In contrast, when present, anti SS-B antibody was always accompanied with anti SS-A antibody and was specific to sicca syndrome patients, although its incidence was lower than that of anti SS-A antibody. Patients with sicca syndrome who had anti SS-A antibody alone or both antibodies developed more severe sicca features of the salivary gland, but extraglandular symptoms were less frequent. In contrast, sicca syndrome patients with anti RNP antibody had mild sicca features of Sjogren's syndrome, and showed clinical characteristics suggestive of connective tissue diseases, including Raynaud's phenomenon and hypocomplementemia. The present study suggests that the detection of anti SS-A, SS-B and RNP antibodies is a useful tool for the diagnosis and the classification of Sjogren's syndrome.