Peripherally administered corticotropin-releasing factor (CRF) inhibits gastric acid secretion in the rat via unknown mechanisms. Because intravenous CRF can produce marked systemic hypotension, the hypothesis that its antisecretory effect is due to a reduction in gastric mucosal blood flow (MBF) was tested. Corpus MBF was measured by hydrogen gas clearance in fasted, urethan-anesthetized rats. CRF (15 nmol.kg-1.h-1 iv) had no significant effect on MBF but significantly decreased systemic blood pressure (BP) by 21.8 +/- 3.4%. This dose of CRF significantly decreased acid secretion stimulated by 40 micrograms.kg-1.h-1 pentagastrin iv but did not decrease MBF despite a 30.3 +/- 2.3% decrease in BP. To avoid the confounding effect of systemic hypotension on MBF, close gastric intra-arterial infusions were performed. CRF (1.7 nmol/h ia) had no effect on BP and did not increase MBF. CRF (3.4 nmol/h ia) slightly decreased BP without modifying MBF. In contrast, histamine (200 micrograms/h ia) significantly increased MBF by 58 +/- 11%. We conclude that 1) the peripheral antisecretory effect of CRF is not related to a decrease in MBF, 2) the maintenance of MBF during CRF-induced hypotension is not due to a direct vasodilator effect of CRF on the gastric microvasculature.