Vivid and bizarre dreams, hallucinations, sleep disturbance and psychosis have all been described following treatment with -Blockers. It has been suggested that these central nervous system (CNS) side-effects are related to the degree of lipophilicity of the -blocker. A randomized double-blind crossover study was performed to compare the incidence of CNS side-effects with atenolol and metoprolol in hypertensive patients who had reported CNS side-effects with lipophilic -Blockers. Eleven women and six men completed the study, in which a 30-item psychiatric questionnaire was used to detect changes in psychological status and possible CNS side-effects. Discontinuation of the original lipophilic -blocker produced a significant improvement in quality of sleep, dreams, concentration, memory, energy, and anxiety. No significant CNS side-effects were reported with atenolol, but introduction of metoprolol caused a significant increase in the incidence of sleep disturbance (p<0.01) and="" restless="" nights="">p<0.05), as="" well="" as="" failure="" to="" achieve="" satisfactory="" sexual="" intercourse="">p<0.05). when="" compared="" with="" atenolol,="" metoprolol="" was="" associated="" with="" a="" significantly="" higher="" incidence="" of="" restless="" disturbed="" nights="">p<0.05). blood="" pressure="" control="" was="" identical="" for="" both="">-Blockers. This study appears to confirm the association between CNS-related side-effects and the lipophilicity of -Blockers.