In the decade since AIDS was recognised in the United States, extraordinary public debate has surrounded the response of the medical establishment, especially the biomedical research enterprise, to the disease. Particular facets of this response have been considered by a number of authors. Gerald M. Oppenheimer, for example, has analysed factors involved in the epidemiological identification of AIDS at the Centers for Disease Control (CDC), and Daniel M. Fox has included biomedical research policy in his identification of a wider ‘crisis of authority’ in the United States health polity. Lacking, however, has been an interpretation of the capacities, policies, opportunities and restraints that governed how and to what extent federal research organisations could respond to AIDS. Although such a full-scale evaluation is far too large for a single paper, we will examine two major policy issues and present two case studies that illuminate the context in which the emerging problem of AIDS was integrated into the existing framework of biomedical research sponsored by the National Institutes of Health (NIH). The two policy issues are the structure of the NIH system for distributing grants and the emergence of targeted disease programmes and planning. The NIH grants system had been constructed carefully over three decades and, when confronted with the AIDS challenge, we will argue, functioned with adequate flexibility within its historic edifice.