The present experiments were undertaken to elucidate the effect of chronic oral administration of clonidine on the endogenous catecholamine metabolism in spontaneously hypertensive rats (SHR). A three month administration of clonidine (20 microgram/kg/day p.o.) produced a slight decrease in blood pressure and heart rate. No significant change was observed in the body weight. A one month administration of clonidine (300 microgram/kg/day p.o.) produced hypotension and weight loss. No significant effect was observed in heart rate. After a two month administration of clonidine (300 microgram/kg/day p.o.), the catecholamine content in the brainstem showed a significant decrease as compared with that in control. 3H-norepinephrine (NE) turnover rate after intraventr culari injection of 3H-NE tended to decrease in the brainstem of SHR while no significant difference was recognized from a view point of uptake, biological half life, elimination rate constant of 3H-NE between control and clonidine administered rats. Under the same experimental conditions, a marked rebound hypertension occurred when medication is discontinued in some cases of this group of SHR.