Systematic energy calculations were performed for a series of LHRH analogs including five agonists with substitutions of D- or N-Me-amino acid residues in positions 4, 6 and 7, and five antagonists with substitutions of D-, N-Me- or alpha-Me-amino acid residues in positions 1, 2, 3, 6, 7 and 10, as well as a bicyclic LHRH antagonist. The geometrical shapes of the calculated low-energy backbone structures for each compound were compared to those of LHRH itself. It appeared that the beta-II' turn at the Tyr5-Gly6-Leu7-Arg8 central tetrapeptide is the common structure for all LHRH agonists considered. LHRH antagonists also possess a common chain reversal in the central tetrapeptide, but it is different from that for LHRH agonists. The LHRH agonists share a similar low-energy conformer at the level of the entire peptide backbone. A characteristic feature of this conformer is a 'surface' formed by a 'polygon' with hydrophobic moieties of pGlu1, Trp3, Tyr5, Leu7 and Pro9 in the corners and with the side chain of the His2 residue in the middle, the latter being crucial for a manifestation of LHRH agonistic activity. Since the N-terminal tripeptide of LHRH presumably participates in a direct interaction with specific receptors, it is legitimate to suggest that the beta-II' turn in the central tetrapeptide maintains the proper spatial arrangement of the N-terminal tripeptide. On the other hand, LHRH antagonists considered in this study were shown to possess low-energy structures, with the spatial arrangement of the residues in the N-terminal tripeptide similar to that of agonists. This would suggest a new approach to the design of LHRH antagonists, namely by stabilizing this specific arrangement, rather than the beta-II' turn in the central tetrapeptide.