Previous investigations have suggested that hydrophilic beta-blockers, which appear at low concentrations in brain tissue, are less likely to produce CNS-related side-effects than are lipophilic beta-blockers, which occur at higher concentrations in the brain. The validity of this hypothesis was tested in a double-blind crossover study in which the hydrophilic beta-blocker atenolol was compared with the lipophilic agents metoprolol and propranolol, in 14 patients with a previous history of nightmares or hallucinations when treated with lipophilic beta-blockers. Nightmares or hallucinations were reported by all patients receiving lipophilic beta-blockers but by only three patients receiving atenolol. The total number of episodes was significantly lower (p less than 0.01) for patients receiving atenolol (8) than for those receiving lipophilic beta-blockers (54). It is concluded that atenolol is significantly less likely to provoke nightmares and hallucinations than are the lipophilic beta-blockers, metoprolol and propranolol. It seems likely that this finding is due to the differences in hydrophilicity amongst these drugs.