Forty-four patients scheduled for lumbar puncture (LP) were recruited to determine the level of penetration of orally administered rufloxacin into cerebrospinal fluid (CSF). The patients were divided into three clinical groups: those with normal CSF (groups A_1d and A_7d), those with aseptic meningitis (group B), and those with bacterial meningitis (group C). Members of group A_1d received a single 400-mg rufloxacin dose, while group A_7d, B, and C constituents had a multiple-dose regimen (one 400-mg dose, followed by one 200-mg dose daily for 6 days). LP was performed on group A_1d members 5 h after they had received treatment, while for group A_7d it was undertaken 5 h after administration of the last dose. For group B, LP was performed 5 h after the first and the last doses, whereas for group C it was undertaken after the first, fourth, and last doses. Concentrations of rufloxacin in simultaneously collected CSF and plasma samples were determined. Mean CSF/plasma rufloxacin concentration ratios ranged from 0.57 to 0.84, depending on the study group. A higher, but not statistically significant, degree of penetration into CSF was observed in patients with bacterial meningitis than in those with normal CSF or aseptic meningitis. These data indicate that rufloxacin diffuses efficiently into the CSF of patients with either inflamed or uninflamed meninges.