In this study, we examined the activity of the tachykinins (TKs) on lamb and sheep isolated gallbladder and whether the TKs are involved in the capsaicin-induced activity in these tissues. Substance P (SP) and physalaemin (PHYS) contracted lamb gallbladder, PHYS-induced striking tachyphylaxis. This tissue was nearly insensitive to neurokinin A (NKA), neurokinin B (NKB), septide, and capsaicin. As in lamb tissues, SP and PHYS both contracted sheep gallbladder although PHYS induced no tachyphylaxis. At doses that had no effect on lamb tissue, NKA, NKB, septide, and capsaicin contracted sheep gallbladder. Our findings indicate that TK receptors differ in adult and young ovine gallbladder. The activity of PHYS on lamb gallbladder could depend on the existence of an unusual binding site, carrying one or more residues critical for the N-terminal sequence present in PHYS but not in SP.