Long-term blood pressure stability in humans is not affected by prolonged hypotensive drug therapy. After withdrawal of long-term hypotensive therapy from essential hypertensives, their blood pressures soon return to pre-treatment levels. Since the well-studied stabilizing systems all adapt to prevailing blood pressure levels, they cannot account for long-term stability of blood pressure, There is a parallel between trough blood pressure and the lower limit of cerebral autoregulation, Blood pressure goes down to a trough level once sleep has been established. This level is maintained for 3-4 h, with minor perturbations. For normal and hypertensive humans and rats, the level is almost the same as the lower limit of cerebral autoregulation, In essential hypertension the nocturnal fall-of blood pressure and the lower limit for cerebral autoregulation could be set by atheromatous narrowing or occlusion of large cerebral arteries, especially those supplying the brain stem, from which the Cushing response is initiated. Constriction and maldevelopment of smaller cerebral arteries are probably the main causes of increased cerebrovascular resistance in spontaneously hypertensive rats (SHR). The structural difference between the two situations might explain the failure of prolonged hypotensive therapy to reduce the lower limit of cerebral autoregulation in humans, which it is able to achieve in young SHR, If trough blood pressure stability were the anchor which prevents casual blood pressures from drifting, a primary increase of cerebrovascular resistance would be a plausible explanation for essential hypertension. It could also make a major causal neurogenic contribution to hypertension in rat models, especially SHR and stroke-prone SHR, I Hypertens 16:907-912 (C) 1998 Lippincott-Raven Publishers.