The circadian rhythm of plasma renin activity during continuous recumbency was determined fifty-one times in thirty subjects who either slept at night or remained awake for 24 h. Both groups had maximum values between 2400 and 0800 h, despite absence of the expected early morning fall in blood pressure, pulse, and glomerular filtration rate in the awake subjects. Infusion of normal saline between 2300 and 0300 h initially suppressed renin, but did not prevent its subsequent rise regardless of the amount of sodium appearing in the urine. Of thirteen patients tested two to five times, twelve had recurrence of the zenith within a single 4 h period on retesting, despite differences in sodium intake, basal blood pressure, and mean plasma renin activity. Peaks of lesser magnitude were also frequently noted, most commonly at 1000 h and 1800–2000 h. Minimum PRA values were not restricted to a particular time of day and did not generally recur at the same time upon retesting. The mean ratio of maximum to minimum PRA in each study was 246% ± 18.3% (±1SEM). The circadian rhythm of renin appears to be independent of known renal mechanisms responsible for regulating renin release. It is possible that this rhythm is controlled by the central nervous system.