Nonmodulation is a process in which there is a disorder in angiotensin-dependent control of the renal circulation and adrenal aldosterone release. The abnormalities are associated with an inability to handle a sodium load and salt-sensitive hypertension. All of the features are corrected by angiotensin-converting enzyme inhibition. A striking family history of hypertension and concordance of responses to angiotensin II in sibling pairs have suggested a familial factor. Genes governing renin substrate (angiotensinogen) production showed gene polymorphisms in nonmodulators. As nonmodulation occurs in approximately 40% of patients with essential hypertension, clearly other genes must contribute.