We have examined the hypothesis that interferon-gamma (IFN-gamma) and its interaction with epithelium may play a role in the perpetuation of inflammation in Sjögren's syndrome (SS). Labial salivary gland primary cell cultures from 16 patients with primary SS (pSS) and eight cultures from patients with SS symptoms but histologically normal biopsies were examined for expression of HLA-DR and cytoplasmic La (SS-B). Epithelial HLA-DR expression was found in 80% of cultures from pSS patients and 38% of those from patients not fulfilling diagnostic criteria. Cytoplasmic La was detected in 50 and 38% of cultures, respectively. Treatment of 14 of the cultures with IFN-gamma increased HLA-SR and cytoplasmic La expression above that of untreated cultures. Depletion of IFN-gamma using neutralizing antibody had the reverse effect. These findings suggest that the perpetuation of chronic inflammation of pSS may be due to the induction of HLA-DR and La antigen expression on epithelial cells by IFN-gamma.