1 This study on 21 neurosurgical patients was set up to investigate the extent to which four chronically administered beta-adrenoceptor blockers, propranolol, oxprenolol, metoprolol and atenolol, cross and blood-brain barrier and enter the cerebrospinal fluid (CSF) and brain tissue. The concentration in the CSF of the three lipophilic beta-adrenoceptor blockers, propranolol, oxprenolol and metoprolol, approximated to the free drug concentration in the plasma, and was a poor predictor of brain concentration. These three lipophilic beta-adrenoceptor blockers appeared in brain tissue at concentrations 10-20 times greater than that of hydrophilic atenolol. The approximate brain/plasma ratio for propranolol was 26, for oxprenolol 50, for metoprolol 12 and for atenolol 0.2. 2 The low concentration of atenolol in brain tissue is possibly responsible for the low incidence of central nervous system-related side effects in patients on this agent compared to lipophilic beta-adrenoceptor blockers.