Sustained human-to-human transmission defines the epidemiological success of seasonal influenza viruses. Although progress has been made in recent years, significant gaps in understanding remain. For example, current evidence suggests that influenza viruses can transmit between hosts through direct contact, the air, or contaminated surfaces, but the relative contributions of these different modalities remain unknown. Critically, each presents very different challenges for prevention. While detailed examination of influenza spread in humans is needed to fully address this and other important knowledge gaps, well-controlled experimental approaches are also essential. We will apply a powerful experimental tool set, including viral genetics and relevant animal models, to unambiguously define the impact of specific host and environmental factors on transmission efficiency. Strong integration with our collaborators focused on the development of improved technology for detection of influenza viruses (Virginia Tech and University of Michigan) will ensure that our animal work can be translated to reduce the public health impact of influenza in humans.