Beagle dogs with catheters chronically implanted into the lateral cerebral ventricle were used to study the distribution of atenolol and metoprolol between the cerebrospinal fluid (CSF) and blood plasma over a 24-hr period during long term treatment. The concentration of atenolol declined more slowly in CSF than in blood plasma and the CSF/plasma ratio of atenolol (after iv administration for 7 days) increased from 0.08 +/- 0.02 (2 hr after dose) to 0.83 +/- 0.14 (24 hr after dose) (mean +/- SD). Furthermore, the CSF concentration of atenolol, relative to the plasma concentration, increased during repeated drug administration. The CSF/plasma ratio 24 hr after an iv dose was 0.48 +/- 0.12 on day 1 and 0.83 +/- 0.14 on day 7. The CSF concentration of the more lipophilic beta 1-adrenoceptor antagonist metoprolol was almost the same as the concentration of the drug in blood plasma. After 7 days of oral treatment, the CSF/plasma ratio of metoprolol 24 hr after dosing was 0.81 +/- 0.10. The regional CSF concentration of atenolol along the neuraxis was determined in anaesthetized dogs after acute iv administration of the drug. The atenolol concentration in CSF from the lateral cerebral ventricle was similar to that in the cisterna magna but lower than the concentration in CSF sampled from the lumbar region. It is concluded that the CSF concentration of the moderately lipophilic beta 1-adrenoceptor antagonist metoprolol equilibrates with the plasma concentration of the drug more rapidly compared with the hydrophilic drug atenolol.