Central nervous system side effects are occasionally associated with the administration of H2-receptor antagonists. There seems to be a direct correlation between the occurrence of side effects such as mental confusion and the drug concentration in the cerebrospinal fluid. In animal experiments the new H2-blocker roxatidine did not cross the blood-brain barrier. We therefore investigated the penetration of roxatidine into human cerebrospinal fluid (CSF). Nine healthy subjects scheduled for elective spinal anesthesia were premedicated with 150 mg roxatidine orally. Blood samples were taken at 30-min intervals for up to 6 h. A 2-ml CSF sample was taken from each patient at the time of spinal puncture. Small amounts of roxatidine were detectable in the CSF, the CSF to plasma ratio ranging from 0 to 0.89.