Ferrets were used as an animal model to study whether controlled transmission of type A influenza is similar to human transmission when sequence changes in HA1 are used as the outcome. Ferrets were infected initially with A/Sydney/5/97 (H3N2) or A/LA/1/87 (H3N2) intranasally, and transmission chains were established by housing infected ferrets with noninfected ferrets with no influenza antibody titer against the infecting virus. Ferrets infected with A/Sydney were seronegative for A/Sydney and A/LA; ferrets infected with A/LA were seronegative for A/LA but had hemagglutination inhibition titers against A/Sydney. Titers of naturally transmitted influenza were higher than those after direct intranasal infection, but lymphocyte counts from nasal washes diminished with transmission. Ferrets infected with A/LA had 2 amino acid differences in HA1 after transmission through 5 ferret cohorts, but those infected with A/Sydney had none. The results show the value of the ferret model. A/LA resembled the transmission of influenza in humans when under antibody pressure.