Immunization of mucosal surfaces has become an attractive route of vaccine delivery because of its ability to induce mucosal immunity. Although various methods of inducing mucosal immunity are being developed, our laboratory has focused on developing adenoviruses as replication–competent and replication–incompetent vectors. The present report will summarize our progress in sequencing the entire bovine adenovirus-3 genome and identifying regions which can be deleted and subsequently used as insertion sites for foreign genes in developing recombinant viral vaccines. Using these recombinant viruses, we demonstrated the ‘proof-of-principle’ in developing mucosal immunity and, more importantly, inducing protection against bovine herpes virus in a natural host–cattle. Finally, we demonstrated that immunity and protection occurred even in animals that had pre-existing antibodies to the vector.