Substance P (SP) and several analogs and fragments have been synthesized and evaluated on non-stimulated and stimulated guinea-pig ileum. In the former test system the potency order was as follows: SP(4--11) greater than SP = [Tyr7]-SP = [Eth11]-SP = [Nle11]-SP greater than [Dala9]-SP greater than SP(7--1) = [Tyr7]-SP(7--11) greater than [Eth11]-SP(7--11) greater than [DAla9]-SP(7--11) greater than [Nle11]-SP(7--11) greater than SP(1--7). The spasmogenic activity of SP and analogs was preserved in the same potency order on stimulated guinea-pig ileum; none of these modifications resulted in an analog with narcotic-like activity. These data are discussed in terms of a hypothetical SP receptor in extravascular smooth muscle.