More than 5,000 primary-care physicians enrolled more than 22,000 patients with mild to moderate hypertension in a postmarketing study in which guanfacine hydrochloride, a centrally acting antihypertensive agent, was given for 28 days. The objectives of the evaluation were: (1) to obtain broad experience with guanfacine for the management of essential hypertension in a clinical practice setting; (2) to obtain information on patient acceptance of guanfacine, 1 mg HS, for the control of essential hypertension; and (3) to obtain more information on the drug's safety in clinical practice. Patients had to be at least 21 years of age, to be receiving a thiazide-type diuretic, and to have a sitting diastolic blood pressure of 95 to 114 mmHg. Women who were pregnant or lactating or planning to become pregnant during the evaluation were excluded. Blood pressure and heart rate were measured before guanfacine was started and at the completion of the study. Adverse on-therapy events were reported at the return visit. The average blood pressure in the general patient population decreased by 17/12 mmHg, that is, from 164/100 to 147/88 mmHg in four weeks. The magnitude of the reduction was not significantly influenced by age, race, sex, duration of hypertension, or the use of concomitant antihypertensive therapy. Adding guanfacine to another antihypertensive regimen resulted in mean reductions of 11 to 15 mmHg diastolic pressure, and the substitution of guanfacine for another antihypertensive agent resulted in mean reductions of 10 to 11 mmHg diastolic pressure. The most common side effect reported was dry mouth in 6% of patients, followed by dizziness, somnolence, fatigue, headache, and nausea, each reported in fewer than 3% of patients. More than 80% of the participants continued to receive guanfacine after the study. Of the total patient population, 7% discontinued guanfacine because of lack of efficacy, 10% because of side effects, and 3% for other reasons. The results of this large postmarketing study confirmed the results of controlled clinical trials conducted prior to marketing.