Three structurally related peptides, ovine corticotropin-releasing factor, sauvagine, and urotensin I are selective mesenteric vasodilators in dogs. To assess the possible benefit of these peptides in nonocclusive mesenteric ischemia, they were compared with a nonselective vasodilator, sodium nitroprusside, in the anesthetized dog. Mesenteric blood flow was reduced by approximately 30%, without lowering of systemic arterial pressure, by either digoxin or pericardial tamponade. In the digoxin model, i.v. infusions of corticotropin-releasing factor, sauvagine, and urotensin I restored intestinal vascular resistance and mesenteric blood flow to control values, without causing a fall in systemic arterial blood pressure. In the tamponade model, only urotensin I was assessed, and it produced the same restoration of hemodynamic variables. On the other hand, in both models, i.v. infusions of nitroprusside, which were effective in correcting intestinal vascular resistance, produced a fall in arterial blood pressure (presumably because of systemic dilatation), which prevented restoration of mesenteric blood flow. Intestinal oxygen uptake was not altered by tamponade, but was reduced by 23% in the digoxin model, where it was restored to control values by both the peptides and nitroprusside. The increased oxygen extraction seen in both models was corrected by the peptides but not by nitroprusside, suggesting that nitroprusside may have a direct and offsetting metabolic effect on the gut.