The involvement of brain dopamine in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied. Intracerebroventricular (i.c.v.) injections of 6-hydroxydopamine (6-OHDA) in young SHR caused depletion of dopamine in frontal cortex and striatum and induced an attenuation of the development of hypertension in SHR. Depletion of noradrenaline and to a lesser extent of serotonin was found as well. The ratio of DOPAC and of HVA to dopamine was increased after 6-OHDA. Pretreatment with the dopamine re-uptake inhibitor GBR-12909 inhibited the effects of 6-OHDA on both blood pressure and brain dopamine content. The effect of 6-OHDA on noradrenaline and serotonin levels were not influenced by pretreatment with GBR-12909. Electrolytic lesions in the substantia nigra delayed the rise in blood pressure in SHR. Lesions in the ventral tegmental area (VTA) were ineffective. After substantia nigra lesions depletion of dopamine was found especially in the nucleus caudatus posterior and the dorsomedial nucleus. After lesions in the VTA substantial dopamine depletion was found in the nucleus accumbens, frontal cortex, lateral septal nucleus and zona incerta. These data suggest that brain dopamine systems play a role in the development of hypertension in SHR and that especially the nigrostriatal system is important in this respect. Moreover, the present results may help to explain the attenuating effect of prehypertensive treatment with 6-OHDA on the development of hypertension.