Twenty-four-hour ambulatory blood pressure (ABP) monitoring was used as a measure of drug efficacy and criterion for inclusion of 29 patients with primary hypertension in a double-blind crossover comparison of the novel cardioselective beta-blocker nebivolol (2.5--10 mg) with lisinopril (10--40 mg) once daily. After 8 weeks of therapy, both regimens reduced clinic BP to a similar and significant extent. Similar and significant reductions in systolic and diastolic ABP in every one of the 24-h periods were observed with both treatments. Moreover, the percentages of "BP loads" were lowered similarly from 64% to 31% and 30% with nebivolol and lisinopril, respectively. Furthermore, a comparable trough:peak ratio of 70% was obtained with both therapies. These data demonstrate that both once daily nebivolol and lisinopril given as monotherapies in patients with ambulatory hypertension provide adequate and similar clinic and ambulatory BP control. In addition, our findings indicate that ABP monitoring may improve the clinical evaluation of new antihypertensive agents.