Objective: To study the local and systemic behavior of the tumor necrosis factor-α (TNF-α) in patients with active uveitis. Methods: TNF-α levels were measured in aqueous humor and peripheral blood samples using an enzyme-linked immunosorbent assay from 23 patients with uveitis and 16 control patients who had been operated on for uncomplicated cataracts. Results: Aqueous humor and sera of patients with uveitis showed higher levels of TNF-α than those of controls (p < 0.001). A comparison of cytokine levels between aqueous humor and sera showed significantly higher levels of TNF-α in serum than aqueous humor (p < 0.001). Correlation studies using the regression test for successive steps showed that serum TNF-α levels correlated with recurrent uveitis (r = 0.4150; p = 0.0489). Conclusions: TNF-α is a cytokine that participates actively in the pathogenesis of clinical uveitis. Our data emphasize the greater systemic than local participation of TNF-α. Finally, an elevated serum TNF-α seems to be associated with a recurrent pattern of uveitis.