1. Sixteen neurosurgical patients received (oral) β-adrenoreceptor-blocking agents (β-receptor blockers) for 3–22 days. 2. Lipophilic β-receptor blockers (propranolol) and metoprolol appeared in cerebrospinal fluid at concentrations similar to the free drug plasma concentration. 3. Cerebrospinal fluid concentrations of β-receptor blockers were poor predictors of brain concentrations 4. Both lipophilic β-receptor blockers appeared in high concentrations in the brain: the brain/plasma ratio was approximately 15:1. 5. Hydrophilic atenolol appeared at low concentrations in brain tissue (about 20 times lower than the lipophilic β-receptor blockers): the brain/plasma ratio was approximately 0.1:1. 6. Central nervous system-related side effects associated mainly with lipophilic β-receptor blockers possibly result from high brain tissue concentrations.