Nine analogs of fusion peptide of influenza virus hemagglutinin whose membrane perturbation activity has been thoroughly tested [Murata et al. (1992) Biochemistry 31, 1986-1992; Murata et al. (1993) Biophys. J. 64, 724-734] were characterized by molecular modeling techniques with the aim of delineating any specific structural and/or hydrophobic properties inherent in peptides with fusogenic activity. It was shown that, regardless of characteristics common to all analogs (peripheral disposition at the water-lipid interface, amphiphilic nature, alpha-helical structure, etc.), only fusion active peptides reveal a specific 'tilted oblique-oriented' pattern of hydrophobicity on their surfaces and a certain depth of penetration to the non-polar membrane core. The conclusion was reached that these factors are among the most important for the specific destabilization of a bilayer, which is followed by membrane fusion.