In order to investigate the mechanisms leading to respiratory depression after lumbar administration of opioids, plasma and ventricular CSF pharmacokinetics of intrathecal meperidine (1 mg.kg-1) were studied in five head-injured patients undergoing surgery for lower limb fracture. Meperidine was detected both in the plasma (arterial catheter) and in the ventricular CSF (intracranial catheter) soon after intrathecal administration: 45 +/- 17 min and 100 +/- 14 min, respectively. The maximal plasma concentration was 341 +/- 133 ng.ml-1, whereas, in ventricular CSF, it was 64.5 +/- 14.9 ng.ml-1. The ventricular CSF-plasma ratio increased with time (r = 0.82) from 0.18 +/- 0.04 at the first hour to 0.38 +/- 0.1 at 16th hour. It is concluded that the putative risk of respiratory depression appears to be mainly related to the absorption into the systemic circulation and to redistribution back into CSF.