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1. The changes of peripheral venous plasma renin concentration (PRC) induced by head-up tilting were studied in four patients with orthostatic hypotension. 2. Two of the patients had the Holmes—Adie syndrome and tests of autonomic function suggested that they had an afferent block from baroreceptors with intact efferent pathways; the others had no evidence of the Holmes—Adie syndrome and investigations suggested that they had interruption of efferent sympathetic pathways. 3. In the two patients in whom lesions of the afferent side of baroreceptor reflexes were suspected, a marked increase in PRC occurred with upright tilting, whereas no change in PRC occurred in the two patients thought to have an efferent sympathetic block. 4. During repeated tilting, supine blood pressure and PRC increased progressively in the two patients with suspected afferent block, but not in the two patients with suspected efferent block. 5. It is suggested that an increase in plasma renin may contribute to the supine hypertension sometimes observed in patients with orthostatic hypotension. 6. It is also suggested that renin release does not require intact autonomic reflexes although certain components of efferent sympathetic pathways, not dependent on baroreceptor reflexes, may be important.