The stainless steel cannula inserting method was used to investigate the effects of angiotensin II on isolated and perfused dog mesenteric arteries with and without indomethacin treatment, or with and without intraluminal saponin-treatment which removed the endothelium. In non-treated preparations, angiotensin II was intraluminally administered repetitively at 10, 20, 30 or 60 min inervals. Each period of angiotensin II causes tachyphylaxis. The order of degree of tachyphylaxis was 10 greater than 20 greater than 30 greater than 60 min intervals. Relatively large doses much readily caused tachyphylaxis. Tachyphylaxis was not affected by phentolamine-treatment preparations. In indomethacin (5 mg)-treated preparations, the angiotensin II-induced tachyphylaxis was significantly less than that in non-treated ones. In small doses of angiotensin II, tachyphylaxis did not appear in the majority of cases in indomethacin-treated preparations. In deendothelial preparations which were induced by intraluminal administration of saponin (1 and 3 mg), the tachyphylaxis was induced similar to non-saponin treated preparations. It is concluded that prostaglandin may partially participate in induction of angiotensin-induced tachyphylaxis, the prostaglandin may be synthesized in the inside of vasculature, and a large dose of angiotensin II induces tachyphylaxis unrelated to production of prostaglandin.