Challenge experiments that induce infections in healthy volunteers are an important method for initial efficacy testing of candidate vaccines and for study of the pathogenesis of infectious diseases. Although these studies can be conducted safely for selected infectious diseases that are either fully treatable or self-limiting, they raise significant ethical issues. An ethical framework is offered for evaluating infection-inducing challenge experiments, which focuses on the scientific and public health rationale for conducting these studies, the risks that they pose and the ways in which these risks can be minimized, the symptoms experienced by healthy volunteers that may cause discomfort or distress, the exclusion of vulnerable research subjects, the informed consent process, the payment of volunteers, and the use of isolation of volunteers to prevent infection of others.