Capsules containing either 16 or 32 mg of14C‐guanabenz were given to 8 hypertensive patients. Maximum concentrations of guanabenz in plasma (1.2 to 5.2 ng/ml) were reached at 2 to 5 hr after dosing.14C elimination into urine was 79.7 ± 10.6% (SD) and 76.7 ± 7.4% of the dose after the 16‐ and 32‐mg doses, respectively, while guanabenz accounted for less than 1% after either dose. Kinetic parameters for guanabenz were estimated by fitting the plasma and urinary data to a 2‐compartment model. After the 16‐mg dose, the elimination half‐life (t½) was 14 ± 5 hr, volume of distribution in the central compartment (Vc) was 5.0 ± 2.2 kl, and total plasma clearance (Clp) was 8 ± 4l/min. After the 32‐mg dose, t½ was 12 ± 3 hr, Vcwas 7.5 ± 1.8 kl, and Clp, was 17 ± 6l/min. No statistically significant difference, except of total plasma clearance, was observed between any of the parameters followed after the 2 doses. (E)‐p‐Hydroxyguanabenz (unconjugated and as a glucuronide) was the major metabolite and accounted for 35.4 ± 3.0% of the urinary radioactivity. Minor amounts of guanabenz and 2,6‐dichlorobenzyl alcohol after β‐glucuronidase hydrolysis indicated thatN‐glucuronidation and cleavage at the benzol carbon were minor metabolic pathways. The drug effectively lowered blood pressure in the hypertensive patients; no other significant effects were noted.Clinical Pharmacology and Therapeutics(19