While renin substrate is increased to values of about 2000–4000 ng 24 hours after simultaneous binephrectomy, the values obtained inpreviously uninephrectomizedorunilaterally ureter ligated ratsare only about 50 to 75 per cent as high (about 1000–2500 ng) 24 hours after removal of the remaining kidney. This decreased reaction is found as early as 30 minutes after uninephrectomy and is still found well over a month later. If the operations (binephrectomy or removal of remaining kidney) are preceded by 17 hourshypoxia, the values in rats whether binephrectomized in one step or in two steps are equally low (600–1700), while pretreatment withoestradiolin both groups results in about equally extremely high values (3500–6000). Previously uninephrectomizedrenal hypertensive ratsshow the same decreased response as normal rats if the untouched kidney is removed before the clipped, but if the clipped kidney is removed before the untouched, the values are as high as those found when both kidneys are removed at the same time. The effect of previous uninephrectomy seems neither related to the decrease in renal renin or to the retention of urinary constituents caused by the op