Initiation of clinical efficacy trials of candidate human immunodeficiency virus (HIV) vaccines may be scientifically and ethically warranted in the next few years. The National Institute of Allergy and Infectious Diseases (NIAID) is making preparations to start trials with minimal delay as soon as a suitable candidate vaccine becomes available. NIAID is sponsoring the establishment of an infrastructure for epidemiological studies of populations at potential sites for such trials. In field trials, we will need to measure suitable end points-infection, immunological status, and clinical status- necessary to judge vaccine effectiveness in preventing infection and/or disease. Difficulties in recruiting and following high-risk populations present a major research challenge. The many scientific, ethical, social, legal, and political issues related to such trials are being addressed in partnership with many groups, both in the United States and abroad. This partnership must include the public and private sectors: communities experiencing epidemic HIV spread, companies developing candidate vaccines, U.S. and international agencies, universities, and governments. Effective HIV prevention will require persistent attention to behavior change, including partner reduction and condom use, even as we develop and test candidate vaccines to prevent HIV and the acquired immunodeficiency syndrome (AIDS).