Critical advances in understanding the pathogenesis and treatment of HIV-1 infection have been made. These include the following: delineation of the replication kinetics of HIV in all stages of disease, underscoring the role of viral replication in disease pathogenesis; development of highly sensitive quantitative assays to determine viral load in infected individuals; and potent new antiretroviral drugs, the availability of which has provided a tool for the investigation of viral pathogenesis and immunopathogenesis, and has permitted the demonstration of the clinical efficacy of combination therapies. The results of studies of potent antiretroviral combination therapies presented at the Fourth Conference on Retroviruses and Opportunistic Infections (January 22-26, 1997, Washington, D.C.) demonstrate that such therapies are capable of at least partially restoring the immune system that is damaged by infection with HIV-1. This includes evidence for the ability of potent therapies to begin to reverse the abnormalities of maturation, activation, and function that are attributable directly or indirectly to the CD4+ helper T lymphocyte population.