Highly active antiretroviral therapy rapidly reduces virus replication in the lymphoid tissue. Production of viral RNA, however, may still be detected in the lymphoid tissue despite negative plasma viremia. Continuing virus production and latent infection in resting cells seem to be important factors for viral rebound following treatment interruption. In parallel with viral suppression, immune activation is decreased and CD4+ T cell counts in the lymphoid tissue increase. It is still not known if there is a potential for complete viral suppression and immune reconstitution. Analyses of the lymphoid tissue during therapy may be helpful in addressing these issues.