We have demonstrated that aerosolized recombinant adenovirus is highly immunogenic when delivered to the lung of rhesus macaques. Specifically, this immunization generates very high levels of persistent CD4 and CD8 T cell responses in the lung, although very low levels throughout the rest of the body. Interestingly, we also find very good generation of antibody responses, both throughout the body and at various mucosal sites. Thus, this route may be very important for the generation of mucosal immune responses needed to protect against challenges such as HIV. But certainly, the high lung cellular responses are ideal for the possible protection against tuberculosis or influenza;we are in the process of immunizing with vectors against these pathogens and testing whether or not protection is seen.