<jats:p>Since both (R)‐ and (S)‐enantiomers of ibuprofen may act on the central nervous system, we investigated their plasma and cerebrospinal fluid (CSF) concentrations in 46 patients with nerve‐root compression pain requiring a lumbar puncture. Each patient received an oral dose of 800 mg rac‐ibuprofen. A single blood and CSF sample was drawn concomitantly from each patient at intervals between 30 min and 8 h after dosing. Both isomers peaked later in the CSF (3 h) than in the plasma (1.5 h). Their CSF concentrations became higher than their concurrent free plasma concentrations after 90 min. The estimated elimination half‐ lives of (R)‐ and (S)‐ibuprofen were 1.7 h and 2.5 h in plasma and 3.9 h and 7.9 h in CSF, respectively. The AUCCSF/AUCplasma ratios (0, 8 h) were 0.009 and 0.015 for the (R)‐ and (S)‐forms, respectively.