A rise in "effective" blood volume and extracellular fluid volume encourages a rise in blood pressure and peripheral resistance, especially if there is renal-mass deficiency. Such a rise diminishes the effectiveness of antihypertensive drugs. An inappropriately high cardiac output leads to high arterial pressure and raised peripheral resistance partly through whole-body "autoregulation" of blood flow. Since this rise in resistance brings the high cardiac output back toward normal, the initial stimulus of the high cardiac output may be difficult to recognize. The kidney has a pivotal role in the hypertensive process through (1) regulation of extracellular fluid volume and (2) probable elaboration of both prohypertensive and antihypertensive humoral agents. Secretion of renin and prostaglandins E2 and F2α is established. Other antihypertensive lipid humoral agents may also be elaborated. The kidney probably participates fundamentally in most hypertensive syndromes.