Cytokines are known to be involved in a number of autoimmune conditions and are increasingly viewed as key components in numerous aspects of normal and abnormal cell functions. The purpose of the present study was to investigate possible immunopathogenic mechanisms within the labial minor salivary glands of patients with primary Sjögren's syndrome (pSS) by examining differential cytokine gene expression in individual cell populations (acini, ducts, or lymphoid cells). A cell-specific microdissection technique in combination with reverse transcription-polymerase chain reaction (RT-PCR) and Southern hybridization using 32P-labeled cytokine gene-specific probes was utilized to measure cytokine messenger RNA expression in individual cell populations of patients and healthy controls. mRNAs for interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and transforming growth factor beta 1 (TGF-beta1) were detected in the epithelial cells (acini and ducts) and lymphoid cells of the labial minor salivary glands of pSS patients. The expression levels of these mRNAs in the epithelial cells were either up- or down-regulated by adjacent focal infiltrating lymphoid cells. mRNAs for all of the above cytokines, with the exception of IFN-gamma, were detected in salivary tissues of healthy volunteers. The epithelial cells in the salivary glands are active participants in the autoimmune-mediated process of pSS, as evidenced by their ability to express a high frequency and wide variety of cytokines. The presence of an infiltrating lymphoid focus within the gland appeared to modulate cytokine gene expression by the salivary epithelial cells.