In general, the natural history of HIV infection as revealed by prospective cohort studies such as the Multicenter AIDS Cohort Study (MACS) is consistent with our current understanding of the immunopathogenesis of HIV disease. Although the limitations of CD4+ T cell counts as a predictor of response to therapy are now recognized, enumeration of these cells remains an important predictor of outcome. Additional information regarding prognosis can be obtained using other immunological and virological information. Analysis of data from cohort studies has revealed varying patterns of CD4+ lymphocyte count decline associated with differing evidence of immune activation, specific antibody responses, CD8+ T cell responses, and level of viral burden. Of interest, some asymptomatic HIV-infected persons appear to show immune stability in the absence of therapeutic interventions. In addition, the combination of antiretroviral therapy and prophylaxis for Pneumocystis carinii pneumonia (but apparently not prophylaxis for fungal or Mycobacterium avium-intracellulare infections) has prolonged survival in patients with AIDS.