ABSTRACT-We characterized the pharmacological nature of the tachykinin receptor subtype mediating the contractile response to electrical transmural stimulation (ETS) in the isolated rabbit iris sphincter muscle preparation by using selective NK,-receptor antagonists, spantide and L-668,169, and a selective NK2-recep tor antagonist, L-659,877. ETS caused a biphasic contraction in this preparation: a rapidly developing cholinergic component followed by a slowly decaying tachykininergic component. The tachykininergic contractile response to ETS was effectively attenuated by spantide and L-668,169, but only slightly by L 659,877, indicating that the tachykinin receptors mediating ETS-induced contraction are of the NK, type. In the same preparation, the contractile activity of substance P (SP) was slightly more potent than that of neurokinin A (NKA). Unlike in other tissues rich in NK,-receptor subtypes, spantide and L-668,169 an tagonized the contractile response to NKA more effectively than that to SP, and the reverse was observed for L-659,877. These results strongly suggest that the tachykininergic contraction induced by ETS in the rab bit iris sphincter preparation is mediated by NK,-receptors which are activated by endogenously released NKA.