Typical features of pneumococcal meningitis have been demonstrated in rats inoculated with Streptococcus pneumoniae. HU-211, a novel noncompetitive N-methyl-d-aspartate antagonist recently demonstrated to inhibit tumor necrosis factor-α production under various conditions, improves recovery in some experimental models of brain injury. The present study tested the efficacy of HU-211 in combination with antimicrobial therapy in reducing brain damage in experimental pneumococcal meningitis. S. pneumoniae-infected rats were treated with saline alone, ceftriaxone alone, or with a combination of ceftriaxone and HU-21118 h after inoculation of the bacteria. Brain edema and blood-brain barrier impairment 48 h after infection were significantly (P < .05) reduced in rats treated with ceftriaxone-HU-211 compared with rats in other treatment groups. The results suggest that HU-211 when given concomitantly with antibiotics attenuates brain damage in the rat model of pneumococcal meningitis.