We investigated the potent non-peptide tachykinin receptor antagonists SR140333 and SR48968 for their ability to prevent the contraction of isolated intestinal tissues elicited by the non-selective agonists substance P (SP) and neurokinin A (NKA), or by [Sar9,Met(O2)11]SP and [beta-Ala8]NKA-(4-10) that are selective agonists for NK1 and NK2 receptors, respectively. In guinea-pig ileum, containing mainly NK1-receptors: SR140333 caused a pseudo-irreversible blockade of contractions induced by either SP (KB, 0.01 nM) or [Sar9,Met(O2)11]SP (KB, 0.03 nM); SR140333 but not SR48968, dose-dependently (IC50, 0.06 nM) antagonized the contractions elicited by capsaicin. In rat duodenum, containing mainly NK2 receptors, SR48968 caused a parallel rightward shift of the concentration-response curves of [beta-Ala8]NKA-(4-10) (pA2, 9.5), but not of NKA. In rat esophageal tunica muscularis mucosae, SR48968 non-competitively antagonized [beta-Ala8]NKA-(4-10) and NKA. SR48968 and SR140333 thus appear to be potent tachykinin receptor antagonists, selective for intestinal receptors respectively of the NK2 and NK1 type. The results also suggest that rat esophagus might contain a NK2-receptor subtype different from that of rat duodenum.