We studied the penetration of cefuzonam (CZON) into the cerebrospinal fluid (CSF) in 20 patients with neurosurgical diseases. Influences of the presence of meningeal reaction and the intensity of brain damage on CSF penetration of CZON were also examined. Concentrations of CZON in serum and CSF were determined using the thin-layer cup method before and 1, 2, 4, and 6 hours after 2 g of CZON was administered intravenously. The serum concentration at 1 hour was 60.4 +/- 31.3 (mean +/- S.D.) microgram/ml, then rapidly decreased to 2.1 +/- 2.3 micrograms/ml at 6 hours. In contrast, the CSF concentration gradually increased, reached a peak level of 0.319 +/- 0.313 micrograms/ml at 4 hours and then slowly decreased to 0.273 +/- 0.249 micrograms/ml at 6 hours. The CSF penetration ration: CZON ([CSF]/[serum]) was 5.6% at 4 hours. The peak CSF concentration in patients with meningeal reaction (0.465 +/- 0.364 micrograms/ml at 2 hours) was about 2-fold higher than that in those without the reaction (0.249 +/- 0.223 micrograms/ml at 4 hours). The peak CSF concentrations in patients with slight, moderate, and severe brain damage were 0.231 +/- 0.133 micrograms/ml at 4 hours, 0.270 +/- 0.232 micrograms/ml at 4 hours, and 0.680 +/- 0.467 micrograms/ml at 2 hours, respectively. CSF penetration of CZON was augmented in patients with meningeal reaction or severe brain damage. These findings indicate that the concentration of CZON in CSF after intravenous administration is sufficient for treatment of meningitis or infections after neurosurgical operations caused by such bacteria as Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae.