In order to study renal tubular handling of two small peptide hormones, [14C]angiotensin II ([14C]AII) and [3H]oxytocin ([3H]OT) were microperfused through rabbit kidney tubule segments in vitro. The reabsorption and tubular sequestration of radioactive label were determined, and the collection fluid was electrophoretically analyzed. The data suggest that [14C]AII is extensively hydrolyzed in the pars recta of the nephron and is rapidly reabsorbed across the tubular epithelium. Under similar experimental conditions, hydrolysis of [3H]OT was not observed in either the proximal straight or cortical collecting tubule segment, and the rate of reabsorption was low. Thus, tubular handling of OT appears to differ from that of AII, probably because of differences in molecular structure.