AbstractThe presence of the sulfur atom of the methionine side chain exerts significant effects at different levels on biochemical behavior of chemotacticN‐formylpeptides. In order to acquire more information on this point, the synthesis, the conformation in the crystal, and the activity of For‐Hse(Me)‐Leu‐Phe‐OMe(2)—an oxygen analogue of For‐Met‐Leu‐Phe‐OMe (f MLP‐OMe) containing theO‐methyl‐L‐homoserine in place of the native methionine at position 1—is reported. The new analogue2adopts a conformation that is extended at the first two residues and folded at theC‐terminal phenylalanine. This conformation is different from that of the parent f MLP‐OMe and strikingly similar to that adopted by f MLP‐OBut. The side‐chain spatial orientation of2corresponds to that adopted by f MLP‐OH when cocrystallized with an immunoglobulin possessing binding properties similar to those of neutrophil receptors. When tested on human neutrophils the formylpeptide2is more active than the parent in the stimulation of directed mobility and maintains both the granule enzyme release activity an the superoxide anion