ANP administered to cirrhotic dogs or chronic caval dogs with ascites and urinary sodium retention (USR) usually causes heterogeneity of natriuretic response. To assess whether this same phenomenon would occur in the absence of edema, ANP at 100 ng/kg/min was given to dogs before and after the induction of USR by a variety of techniques. Eight dogs were over-diuresed with furosemide over a 2-day period, and 9 dogs were subjected to subacute hemorrhage over a similar period. These dogs were retested with ANP one day later. All 8 dogs given furosemide showed no response to ANP (DELTA-U(Na) V = 7.4 +/- 4.8-mu-Eq/min), compared to a normal response prior to the diuretic (DELTA-U(Na) V = 128 +/- 34-mu-Eq/min). The 9 hemorrhaged dogs also responded normally to ANP prior to this manipulation (DELTA-U(Na) V = 74 +/- 14-mu-Eq/min), but a blunted response post-hemorrhage (DELTA-U(Na) V = 35 +/- 13-mu-Eq/min). This profile was made up of 5 dogs who responded to ANP (DELTA-U(Na) V = 62-mu-Eq/min) and 4 who had no response whatsoever (DELTA-U(Na) V = 3-mu-Eq/min). When 8 dogs were given USR because of continuous mineralcorticold administration, none responded, but all had a magnified natriuretic response to ANP during the 'escape' phase. Eight dogs were administered minoxidil (10 mg) by mouth daily to induce USR. All 8 dogs responded to ANP (DELTA-U(Na)V = 93 +/- 6-mu-Eq/min) which was no different from the pretreatment response (DELTA-U(Na) V = 65 +/- 3-mu-Eq/min). We conclude that heterogeneity of natriuretic response to ANP may be seen in some causes of USR without edema (hemorrhage) but is not a uniform property of the sodium-retaining nephron.