The haemagglutinin (HA) protein of influenza determines the type of target cell that the virus can infect. By mutating the site of the HA that binds to sialic acids in receptors on target cells, which differ between avian and mammalian cells, and other protein regions that determine the pH at which virus–cell fusion can occur, researchers have generated viruses that have avian HA proteins that can be transmitted from mammal to mammal. a, Imai et al.1 identify four mutations (N158D, N224K, Q226L and T318I) in the HA of a highly pathogenic avian influenza virus, H5N1, that allow a virus with this HA to be transmitted by respiratory droplets between ferrets. The receptor-binding site of the HA is shaded in yellow. b, Chen et al.5 also created a virus with an H5N1 HA that can be partially transmitted between ferrets, by introducing three mutations (Q196R, Q226L and G228S) into the H5 HA. The virus used as the basis for this hybrid already contained the N158D mutation that Imai and colleagues also identified in their mutated HA. c, Sorrell et al.7 used the HA protein from a low-pathogenic H9N2 avian virus to achieve similar transmissibility. The Q226L mutation was already present in this virus, and two additional mutations (T189A and H192R/HA2) were acquired during ferret infection studies. The H192R/HA2 mutation cannot be shown because the protein is cleaved at a site that lies in front of this amino-acid residue. Full virus names and their subtypes are given below each structure. Mutated amino-acid residues are indicated by red and blue spheres.