The antihypertensive effect and side-effects of the new centrally acting agent guanfacine (BS 100-141, Estulic) and guanethidine (Ismelin) were compared in a single-blind, cross-over study. The study consisted of two active treatment periods of 6 weeks each, both preceded by a 1-3 weeks placebo period. 2. Sixteen ambulant patients (six male, ten female) with mild or moderate hypertension were admitted to the study. The patients were also receiving diuretic therapy (clopamide 10-20 mg daily). On average the optimal daily dose of guanfacine was 3 mg and of guanethidine 20 mg. 3. An equally large and significant decrease in blood pressure was produced by both drugs. Both guanfacine and guanethidine caused a very slight reduction in heart rate. Mild orthostatic hypotension occurred in 11 patients during guanethidine therapy. Dryness of the mouth occurred in 13 patients taking guanfacine.