['It has been demonstrated that there are structural and functional similarities between interferon-alpha (INF-alpha) and endorphins. We have reported that there are distinct domains in the IFN-alpha molecule that mediate immune and analgesic effects, respectively, and that the opioid-like analgesic effect of IFN-alpha is mediated by the mu opioid receptor, thus inferring that the analgesic domain of IFN-alpha consists of Tyr(122) and the residues around Tyr(122) in the tertiary structure. The aim of this work was to further explore the molecular basis for the analgesic domain of IFN-alpha.', 'By using site-directed mutagenesis, the structure of IFN-alpha was changed and a mutant of IFN-alpha was obtained. Then, the antiviral activity and opioid-like analgesic activity of IFN-alpha were measured.', 'When the Pro(39) residue of IFN-alpha, which is located close to the Tyr(122) residue in the tertiary structure, was mutated to Gly, the analgesic activity of this mutant was lost completely, but the antiviral activity of IFN-alpha was maintained compared with wild-type IFN-alpha.'] Does the analgesic domain of interferon-alpha2b contain an essential proline ( 39 ) residue?