Previously we reported that immunoreactive angiotensin II (Ang II) release from isolated perfused rat mesenteric arteries was mediated by β-adrenergic receptor activation. However, the precise mechanism of regulation of vascular renin-angiotensin is not completely understood. In this study, we examined the effect of indomethacin and medofenamate on immunoreactive angiotensin I (Ang I) and Immunoreactive Ang II release from perfused rat hind leg vasculature to delineate the possible relevance of prostaglandins to the vascular renin-angiotensin system in vitro. We also examined the effects of isoproterenol and propranolol on the immunoreactive Ang I and II release. Isolated rat hind legs were perfused with Krebs-Ringer solution, and immunoreactive Ang I and II released into the perfusate were measured directly by using a Sep-Pak CSs18cartridge connected to the perfusion system. Indomethacin and meclofenamate (10−8to 2 × 10−6M) added to the perfusion medium suppressed immunoreactive Ang I and II release to similar extents in a dose-dependent manner (p< 0.001); the maximal percent inhibition of immunoreactive Ang II release evoked by these Inhibitors (2 × 10−6M) was 60 ± 6% {p< 0.001) for indomethacin and 50 ± 4% (p< 0.001) for meclofenamate. Isoproterenol (10−6M) failed to cause a change in the release of both pep tides, but propranolol (10−6M) slightly decreased the release of immunoreactive Ang I and II by 28 ± 4% (p< 0.001) and 32 ± 4% (p< 0.001), respectively. There was a highly significant positive correlation between the released amount of immunoreactive Ang I and that of immunoreactive Ang II altered by indomethacin (r= 0.91), meclofenamate (r= 0.94), or propranolol administration (r= 0.90). These results suggest that the renin-angiotensin in the hind legs is modulated by prostaglandins and that a difference exists in the β-adrenergk receptor-mediated release of Ang II among diverse vascular beds.