By inducing both adhesion and migration of lymphocytes, chemokines play an important role in immune and inflammatory responses. To learn how these processes promote disease, we have examined the activities of chemokines in the lacrimal glands (LG) of nonobese diabetic (NOD) mice, an animal model of Sjogren's syndrome (SS). The expression of three molecules in the chemokine superfamily, RANTES, IP-10 and lymphotactin, correlated with the local recruitment of lymphocytes into the LG of NOD mice. Both RANTES and IP-10 gene transcripts were first detected in these LG when the mice were 8 weeks of age and amounts increased markedly during the course of active disease; lymphotactin mRNA was also expressed but at lower levels. In situ hybridization of LG indicated that lymphocytic cells in the inflammatory infiltrates were responsible for the production of RANTES and IP-10. Concomitant with the induction of chemokine expression was the appearance of cellular receptors for RANTES (CCR1, CCR5) and IP-10 (CXCR3). Furthermore, anti-RANTES treatment significantly reduced inflammation in the LG from NOD mice. In the SS-like disease of NOD mice, this distinct pattern of activity provides evidence for the contribution of these components to site- and time-specific recruitment of lymphocytes in the characteristic destruction of glandular structures.