Objective: The purpose of the study was to investigate interleukin-6 (IL-6) levels in the tear fluid and sera of patients with Sjogren syndrome (SS). Participants: Twelve patients with primary SS and 12 normal control subjects participated. Intervention: Tear fluid and sera were obtained from the study and the control groups. Evaluation of tear fluid and sera IL-6 levels was done by using a quantitative enzyme-linked immunosorbent assay kit. All assays were carried out blindly with respect to diagnosis. Main Outcome Measures: Tear fluid IL-6 levels were measured. Results: The mean concentration (± standard error) of IL-6 in the tears of patients with SS was elevated significantly compared to that of normal control subjects (88.6 ± 16.2 vs. 42.1 ± 10.6 pg/ml; P < 0.05). No significant differences were noted in the serum IL-6 levels between the two groups. A significant correlation (r = 0.742, P = 0.006) was found between tear fluid IL-6 levels and the focus score of lip biopsy specimens in patients with SS. Conclusion: Tear fluid IL-6 levels may serve as an important marker for tear gland involvement in SS.