Previous studies provide conflicting conclusions concerning the consequences of abrupt withdrawal of guanabenz therapy for essential hypertension. In the present study, 10 patients were treated for mild to moderate essential hypertension for 12 weeks, following which the drug was abruptly withdrawn. Blood pressure, pulse rate, and plasma catecholamine levels were obtained before, at 4 and 12 weeks after starting therapy, and 48-96 h and 4 and 8 weeks post-therapy. At the end of 12 weeks of therapy, the mean dose of guanabenz was 22.2 +/- 4.4 mg/day (range, 16-48 mg/day) and supine blood pressure was 140 +/- 5.5/88 +/- 2.4 mm Hg. Two to 4 days after drug withdrawal, supine and standing diastolic blood pressure remained significantly reduced compared to control (p less than 0.01). Standing systolic blood pressure also remained significantly reduced compared to control (p less than 0.01). Mean plasma catecholamine level was less than baseline after 4 weeks of therapy, but the change was not significant. No increase in plasma catecholamine concentration was observed at any time during the withdrawal period. No patient had symptoms of sweating, nervousness, palpitations, or insomnia after guanabenz withdrawal. In one patient with pretreatment systolic pressure of 150 mm Hg, systolic pressure 48 h after drug withdrawal was 160 mm Hg. These studies, together with previous reports, suggest that guanabenz therapy for mild to moderate essential hypertension in doses of 32 mg/day or less can be safely withdrawn on an outpatient basis with a very low incidence of withdrawal phenomena.