To investigate the role of the N-terminal region of the heptapeptide FMRFamide-like peptide, pQDPFLRFamide, three analogues were synthesized. The analogues [pQNPFLRFamide, pQDAibFLRFamide (Aib = aminoisobutyric acid) and pQDGFLRFamide] contained modifications at amino acid residues 2 and 3, which we believed might be critical for maintaining the bioactive conformation of the heptapeptide. The analogues were tested for their ability to bind to receptors in membranes from Helix aspersa circumoesophageal ganglia and for their biological effects on the isolated Helix heart, the Helix tentacle retractor muscle, and extensor-tibiae neuromuscular preparation of the locust. Schistocerca gregaria. The substitution of Asn for Asp2 and that of Aib for Pro3 were conservative with respect to retention of heptapeptide-like biological activity, whereas the substitution of Gly for Pro3 significantly improved the binding affinity of the peptide for the FMRFamide receptors and conferred on the peptide some characteristic FMRFamide-like biological activity. Thus, pQDPFLRFamide bioactivity may depend on a bent conformation in solution.