Evidence of selective inhibition, differences in dose-response relationships, and cross-tachyphylaxis studies suggest that separate receptors and/or mechanisms may be involved in responses to angiotensin (Ang), [Sar1]Ang II, and Ang III (= des-Asp1-Ang II). The extracellular Ca2+ requirement for contractile responses induced by angiotensin peptides and norepinephrine was determined in rabbit aortic strips. Responses to K+ and [Sar1]Ang II were attenuated markedly by treatment with SKF-525A, verapamil, or Ca2+-free buffer. The response to Ang II was not impaired by verapamil, was blocked partially by SKF-525A, and was reduced markedly in Ca2+-free medium. Norepinephrine- and Ang III-induced contractions were not dependent on extracellular Ca2+. K+, Ang II, and [Sar1]Ang II required extracellular Ca2+ to induce contraction of the rabbit aorta. The data indicate that Ang III may have a mechanism of action that differs from that of [Sar1]Ang II and Ang II.