Following nephrectomy, the disappearance of endogenous renin from the circulating vascular volume was studied in man and dog. In each species there was a fast and a slow component to the disappearance curves. Mean half-times of the fast and slow component were 13±1.1 and 280±94.7 min in men, while in dogs they were 9.7±3.0 and 93±17.3 min, respectively. The disappearance of renin from dog plasma and whole blood incubated in vitro was also studied. There were 2 exponential components to the disappearance curves from whole blood, while there was only 1 component to the disappearance curves from plasma. The in vitro half-life of renin disappearance from whole blood was considerably longer than that observed in vivo, supporting the view that some organ or organs play a role in the inactivation of renin in the body. To explain the distribution and disappearance of renin, the data were analyzed on the basis of 2-compartment system. The findings suggest that the rapid component of the disappearance curve of renin may represent its distribution into a non-plasma compartment from the plasma compartment, while the slow component may represent its metabolic degradation.