We establish that the cultivation of influenza (H3N2) virus from any infected individual in chicken embryos (eggs) can result in the isolation of viruses with antigenic and/or structural heterogeneity in the hemagglutinin (HA) molecule. This variability contrasted sharply with the apparent lack of antigenic alterations in the HA of influenza viruses isolated from patients in Madin Darby canine kidney (MDCK) cells. The most common subpopulation of egg-grown influenza viruses had the same phenotype as MDCK cell-grown virus and may best represent the virus circulating in humans. It should be considered the optimal strain for use in vaccine and epidemiologic studies. © 1989.