This study compared the effects of atriopeptin III (AP III) on sodium excretion and renal interstitial hydrostatic pressure (RIHP) in control rats and in rats pretreated with 2-bromoethylamine (BEA) to produce papillary necrosis. In control rats, infusion of AP III (100 ng.kg-1.min-1) increased sodium excretion from 2.2 +/- 0.7 to 6.4 +/- 0.9 microeq.min-1.g kidney wt-1 and RIHP from 6.8 +/- 0.7 to 8.7 +/- 0.9 mmHg, whereas glomerular filtration rate and renal blood flow were unaltered. Similar results were obtained in rats pretreated with BEA 48 h before the experiment. In rats studied 6 wk after BEA treatment, the papilla was absent and there was atrophy of juxtamedullary nephrons. AP III did not alter sodium excretion or RIHP in this group of rats. These results indicate that 1) an intact renal papilla and/or juxtamedullary nephron population may be required for the natriuretic effect of AP III; 2) the papillary injury 48 h after BEA is not sufficient to abolish the natriuretic response to AP III; and 3) elevations in RIHP may play a role in the natriuretic response to AP III.