Salivary and lacrimal gland secretions are reduced in primary Sjögren's syndrome (pSS). Aquaporins (AQPs) are involved in transmembrane water transport, and different isoforms show specific cellular and subcellular distributions in salivary and lacrimal glands. Changes in expression of AQP molecules have therefore been suggested to contribute to the glandular dysfunction in pSS. AQP-5 is present in the apical membrane of acinar cells, where it mediates fluid outflow; however, we have recently shown that its expression is not altered in pSS. We therefore studied whether expression of other isoforms of AQP would be altered in pSS. Using high-resolution confocal microscopy, we determined the distribution of AQP-1 and AQP-3 in labial salivary gland biopsies from 11 patients with pSS and 9 healthy controls. AQP-1 is present in myoepithelial cells surrounding acini, and its expression in these cells was decreased by 38% in pSS glands. By contrast, expression of AQP-1 in endothelial cells of nonfenestrated capillaries was not altered in pSS. AQP-3 was expressed in the basolateral membrane of acinar epithelial cells, and its expression was not altered in disease. We therefore conclude that AQP-1 expression in myoepithelial cells is selectively down-regulated in pSS and that myoepithelial cell dysfunction may play a crucial role in the pathology of this disease.