In order to evaluate the role of the sympathetic nervous system in the development and maintenance of spontaneous hypertension, spontaneously hypertensive and normotensive rats were give 6-hydroxydopamine (6-OH-dopamine). A single i.v. dose of 6-OH-dopamine (100 mg/kg) caused a biphasic rise in blood pressure in both hypertensive and normotensive rats. During long-term treatment the first dose of 6-OH-dopamine (25 or 50 mg/kg i.v.) lowered the blood pressure, measured 24 h after injection, two or three times more in hypertensive than in normotensive rats. As a result, the blood pressure reached the same level in both groups, i.e. 90–100 mm Hg. Within three days this hypotension subsided. After repeated weekly administration of 6-OH-dopamine the depressor effect declined gradually and after 4 weeks it was no longer significant. When this stage was reached, adrenal demedullation as such neither lowered the basal blood pressure, nor prevented the development of tolerance to 6-OH-dopamine. Accordingly, the adrenal medulla is not decisive in maintaining the blood pressure and in the development of tolerance to the depressor effect of 6-OH-dopamine in spontaneously hypertensive and normotensive animals. After treatment with 8 weekly doses of 6-OH-dopamine, the pressor response to noradrenaline increased in both hypertensive and normotensive rats, while the response to tyramine decreased. When, on the second day after birth, new-born rats of the hypertensive strain were given a single dose of 6-OH-dopamine (50 mg/kg i.p.) the development of hypertension was inhibited to some degree. This inhibition was more marked when the animals were given weekly doses of 6-OH-dopamine (50 mg/kg i.p.) during 5 weeks. On the other hand, when pregnant rats of the same strain received 6-OH-dopamine (50 mg/kg i.v.) twice during the last week before delivery, the offsprings did develop hypertension. It is evident that the adrenergic nervous system plays an important part in the development of hypertension in rats of a spontaneously hypertensive strain, but it is no longer of essential importance once the hypertension is established.