The central nervous system subserves the homeostasis of the circulation and is organized as a negative feedback system. The following properties of such a feedback system are of interest: a) the setting; b) the range of the regulation; and c) the nature of the feedback (regulated) variable. In this review we show that in hypertension blood pressure is set at a higher level, but regulation of blood pressure in hypertension is normal. The central nervous system is involved in maintaining a higher set point in early human hypertension as well as in many forms of experimental hypertension. Results from trials of antihypertensive drugs suggest that setting of the baseline level of blood pressure and regulation of blood pressure variability are independent properties and are probably regulated by different areas of the central nervous system. It is, therefore, unlikely that research on blood pressure "reactivity" will elucidate the pathophysiology of the central resetting of baseline blood pressure level in hypertension. We present evidence that in subserving the circulation, the central nervous system regulates and senses blood pressure and not flow. Pathophysiologic implications of this concept are discussed particularly in regards to the apparent decrease of sympathetic tone during the evolution of hypertension.