Conformational energy analyses were carried out on the chemotactic tripeptide fMLF (CHO-Met-Leu-Phe) and three analogs fALF (CHO-Ala-Leu-Phe). fMF (CHO-Met-Phe), and MLF (H-Met-Leu-Phe). A near-folded or puckered conformation predominates in all four peptides. The calculated average end-to-end distance R of each of the peptides is 7.4 A, 7.6 A, 7.0 A, and 7.3 A, respectively (where bends have R less than or equal to 7 A and extended structures have R approximately 10.5 A). The puckered conformation calculated for fMLF is similar to that determined experimentally for fMLF in nonpolar solvents and in the protein receptor. The results suggest that maximum chemotactic activity of the peptides depends on a combination of the chemical structure (the presence of N-formyl-methionine) and backbone conformation (C7conformation of the first amino acid residue).