By applying the d-test to large viral phylogenies, we infer sites in the gp160 protein (encoded by the env gene) of HIV-1 that have undergone a change in the relative fitness of different amino acids between two strains representative of two highly divergent HIV-1 subtypes; and sites in the hemagglutinin (HA) protein of influenza A that have undergone such a change between two strains representative of two influenza subtypes. The gene discussed is ENPEP; the disease is influenza.