Limited data on the relative contributions of different routes of transmission for influenza virus are available. Person-to-person transmission is central to seasonal and pandemic spread; nevertheless, the modes of spread are a matter of ongoing debate. Resolution of this discussion is paramount to the development of effective control measures in health care and community settings. Using the guinea pig model, we demonstrated that transmission of influenza A/Panama/2007/1999 (H3N2) virus through the air is efficient, compared with spread through contaminated environmental surfaces (fomites). We also examined the aerosol transmission efficiencies of 2 human influenza virus A strains and found that A/Panama/2007/1999 influenza virus transmitted more efficiently than A/Texas/36/1991 (H1N1) virus in our model. The data provide new and much-needed insights into the modes of influenza virus spread and strain-specific differences in the efficiency of transmission