Problem: One of the most serious complications of bacterial meningitis, particularly in childhood, is sensorineural hearing loss; yet the mechanism of this hearing loss is not clearly understood. It is also known that the levels of TNF- a and IL-1 a in CSF are significantly elevated in bacterial meningitis patients. This study was designed to evaluate the role of nitric oxide (NO) in the ototoxic effect of TNF- a and IL-1 a and L-NAME injected into the CSF of guinea pigs.Methods: Twenty-six guinea pigs (52 ears) were randomly assigned into 6 groups consisting of control group, L-NAME group, TNF- a group, TNF- a + L-NAME group, IL-1 a group, and IL-1 a + L-NAME group.The thresholds of auditory brain stem response (ABR) were measured before as well as 6 and 24 hours after the administration of the cytokines. TNF- a and IL-1 a were directly injected into the cisterna magna in a dosage of 0.1 i g in 10 ig/ml concentration. L-NAME, NO synthase inhibitor, was injected intraperitoneally 30 minutes prior to the administration of cytokines. Scanning electron microscopy (SEM) was used to find the morphological damage of hair cells.Results: In TNF- a group, the ABR threshold at 6 and 24 hours after the injection was 19.2 3410.2 dB, 18.3 3410.3 dB; in the TNF- a + L-NAME group, 3.3 342.6 dB and 8.3 344.1 dB; in the IL-1 a group, 6.9 344.6 dB and 11.25 348.3 dB; in the IL-1 a + L-NAME group, 1.7 342.7 dB and 1.3 342.5 dB, respectively. The outer hair cell damage in the second and third rows was noted in the TNF- a and IL-1 a groups.Conclusion: This study suggests that the sensorineural hearing loss associated with bacterial meningitis may be caused in part by the actions of proinflammatory cytokines such as TNF- a and IL-1 a. The hearing loss may be mediated by NO and it can be prevented by L-NAME.Significance: Hearing loss induced by bacterial meningitis can be prevented partly by L-NAME.Support: None reported.