The genome projects of the past decades have created extensive databases of biological information with applications in both research and education. We describe an inquiry-based exercise that uses one such database, the National Center for Biotechnology Information Influenza Virus Resource, to advance learning about influenza. This database contains genomic sequences of virus ranging from the strains that caused the 1918 pandemic and subsequent seasonal cycles of influenza, as well as the H1N1 “swine” flu, which has recently caused pandemic disease, and the H5N1 “avian” flu, which remains a potential threat. The web interface to this database allows retrieval of gene and protein sequences from selected strains of virus, alignment of these sequences, and construction of evolutionary trees. In this exercise, students develop hypotheses about the epidemiology or evolution of influenza originating from species, locations, or time periods. The hypotheses are tested by retrieving sequences from specified viral strains and constructing an evolutionary tree to visualize the origin of these strains. We describe the use of this exercise in a human biology course for nonscience majors as part of a unit about influenza.