Analogues of [Orn6]‐SP6‐11have been synthesized in which the Met11residue is replaced by glutamate γ‐alkylesters. These analogues were tested in threein vitropreparations representative of NK‐1, NK‐2, and NK‐3 receptor types. Substitution of the SCH3group of the Met11side chain by a COOR (R = methyl, ethyl, n‐propyl, n‐butyl, cyclohexyl) group results in analogues which are full agonsists in NK‐1 and NK‐2 preparations but show little agonist activity in the NK‐3 preparation. When the SCH3group is replaced by a t‐butyl ester group and the resulting analogue is a full agonist in all the above preparations and more active than the parent hexapeptide and SP‐OCH3at NK‐1 receptors. It is concluded that for activity at NK‐1 receptors methionine can be replaced by γ‐t‐butyl glutamate without loss of activity, whilst at NK‐2 and NK‐3 receptors the above substitution increases the activity of [Orn6]‐SP6‐11. Other γ‐alkyl esters of th