Six substanceP (SP) analogs substituted by D-homoglutamine (Hgn) at position 5 or/and 6 were prepared by the solid phase method. The activity of the peptides was assayed on the smooth muscles of the isolated guinea pig ileum and trachea. Results indicate that the substitution of D-Hgn for Gin residue(s) reduces the activity. [D-Hgn6]-SP (4–11) 5 acted as an antagonist of SP.