AN antigenic relationship has been established between A/equi-2 influenza virus isolated in 1963 and the 1968 Hong Kong variant of human type A2 influenza virus1. This relationship suggests that the Hong Kong variant was derived from the equine virus. To evaluate this relationship further and to test the possibility of an exchange of viruses between species we have carried out virus challenge studies with normal volunteers. Here we describe the occurrence of clinical syndromes similar to those described for naturally occurring influenza after inoculation of antibody-free volunteers with a strain of influenza A/equi-2 virus.