Recent research advances have afforded substantially improved understanding of the biology of HIV infection and the pathogenesis of AIDS. With the advent of sensitive tools for monitoring HIV replication in infected persons, the risk for disease progression and death can be assessed accurately and the efficacy of anti-HIV therapies can be determined directly. Furthermore, when used appropriately, combinations of newly available, potent antiviral therapies can effect prolonged suppression of detectable levels of HIV replication and circumvent the inherent tendency of HIV to generate drug-resistant viral variants. However, as antiretroviral therapy for HIV infection has become increasingly effective, it has also become increasingly complex. Familiarity with recent research advances is needed to ensure that newly available therapies are used in ways that most effectively improve the health and prolong the lives of HIV-infected persons. To enable practitioners and HIV-infected persons to best use rapidly accumulating new information about HIV disease pathogenesis and treatment, the Office of AIDS Research of the National Institutes of Health (NIH) sponsored the NIH Panel To Define Principles of Therapy of HIV Infection. This Panel was asked to define essential scientific principles that should be used to guide the most effective use of antiretroviral therapies and viral load testing in clinical practice. On the basis of detailed consideration of the most current data, the Panel delineated 11 principles that address issues of fundamental importance for the treatment of HIV infection. These principles provide the scientific basis for the specific treatment recommendations made by the Panel on Clinical Practices for the Treatment of HIV Infection sponsored by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation. The reports of both of these panels are provided in this supplement. Together, they summarize new data and provide both the scientific basis and specific guidelines for the treatment of HIV-infected persons. This information will be of interest to health care providers, HIV-infected persons, HIV and AIDS educators, public health educators, public health authorities, and all organizations that fund medical care of HIV-infected persons.