We have compared clinical (Schirmer I test, BUT and rose bengal staining), laboratory (lysozyme and lactoferrin tear levels) and histological tests (impression cytology) in 165 eyes from 85 patients with primary Sjögren's syndrome and in 80 eyes from 40 control subjects. Impression cytology can provide the location of cellular alterations on the ocular surface and information on the severity of the disease. The upper bulbar and interpalpebral areas from patients with primary Sjögren's syndrome were shown to have cellular alterations early in the course of the disease, while the lower bulbar and lower palpebral areas were only affected in severe cases. Statistical analysis has shown that impression cytology and rose bengal staining are the most specific and sensitive methods for the diagnosis of primary Sjögren's syndrome.