The levels of tumor necrosis factor (TNF)-alpha in cerebrospinal fluid (CSF) were analyzed in 139 patients with meningitis and in 20 control subjects. Elevated concentrations were observed in 42 (82%) of 51 patients with purulent bacterial meningitis (18/24 Haemophilus influenzae, 13/14 Streptococcus pneumoniae, 7/7 Neisseria meningitidis, and 4/6 with other purulent bacterial etiology). In contrast, elevated levels were found in only 5 of 78 individuals with nonbacterial meningitis (2/8 with herpes simplex type 2, 3/3 with varicella-zoster virus). Thus, the positive and negative predictive values were 0.89 for indicating a purulent bacterial meningitis. Raised CSF TNF alpha levels were observed in 7 of 8 patients with purulent bacterial meningitis in whom the routinely used parameters did not unequivocally indicate the diagnosis. Moderately increased levels were seen in 5 of 6 patients with Mycobacterium tuberculosis meningitis and in 1 of 4 cases of Borrelia burgdorferi. Thus, the present study indicates that concentrations of TNF alpha in CSF usually can discriminate between purulent bacterial and nonbacterial meningitis. These findings may contribute diagnostic guidance with routinely used CSF parameters.