Renal function was investigated in non-hydrated normal dogs and in dogs with slight isotonic hypervolaemia before and after increasing the excreting renal mass by connecting a pair of isolated kidneys into their circulation. After connecting the isolated kidneys to the perfusor's circulation, the excreting capacity of the in situ kidneys decreased markedly in both groups, without any change in the arterial blood pressure. Their urine output calculated for 100g kidney weight dropped from 0.52 +/- 0.43 to 0.30 +/- 0.18 ml/min in the non-hydrated group, and from 2.3 +/- 1.17 to 1.33 +/- 0.96 ml/min in the hydrated one. The urine flow of the isolated kidneys was 0.29 +/- 0.12 ml/min in the non-hydrated and 1.11 +/- 0.53 ml/min in the hydrated animals. Sodium excretion displayed similar changes. The findings suggest, that the excretory capacity of the kidneys and its distribution between the two kidneys is regulated very precisely. In our opinion, one or more "natriuretic factor" may be responsible for this precise regulation. The supposed factor seems to be produced extrarenally, and is only "used up" by the kidneys. It appears to exert its effect on the tubular part of the nephron, regulating the permeability of the tubular wall and controlling in this way the reflux of sodium and water from the capillary side to the tubular lumen. The decreased excreting capacity of the kidneys is attributed to an increased consumption of the natriuretic factor by four kidneys.