Secure access to food, adequate in quantity and quality, is becoming increasingly problematic for many. The number of food insecure is rising worldwide, reaching more than 1 billion according to the latest estimate (FAO 2009). Falling incomes, in part due to the global financial crisis, and continuing high food prices are proving devastating for those whose livelihoods are the most precarious. Climate change and variability are contributing to food insecurity in Africa and other regions and will do so increasingly in future. The most vulnerable are those dependent on highly seasonal, rainfed agriculture (IPCC 2007). The impact of rising levels of hunger on human health and particularly major diseases such as HIV/AIDS, tuberculosis and malaria is of wide concern. However, our ability to predict with confidence is limited. With respect to HIV/AIDS, much of what is known about the effect of hunger and other facets of poverty comes from cross-sectional or longitudinal studies of limited duration and with few survey rounds that shed little light on dynamic effects, whether trends or cycles, and give little insight into the impact of major shocks (Gillespie et al. 2007). The fact that hunger is both a cause and a consequence of HIV/AIDS further limits the ability of these methods to disentangle the effect of change in any one. The evidence reported here brings new light to bear on this question. It assesses the 2001-03 famine in Malawi as a country-scale natural experiment on the effect of hunger on the dynamics of HIV. The famine has been described as a particularly severe seasonal hunger event (Devereux et al 2008) and thus it also brings into sharper relief the links between seasonal hunger and HIV risks. Mervyn Susser (1981) defined natural experiments as “observational studies of the effects of sharp, well-defined but unplanned changes in which exposed and unexposed comparison groups can be readily identified”. The famine in Malawi can be fairly well delimited in time and, beyond exposed and unexposed, the degree to which different groups were exposed can also be defined. As described below, the extent of hunger varied among rural areas and between them and urban areas. Hunger was also experienced differently by men and women. Natural experiments have a long history in epidemiology and in particular have provided crucial insights into the consequences of sharp reductions in food intake imposed on whole populations or large groups (Apfelbaum 1946, Stein et al. 1975, Franco et al. 2007). While the interventions that underlie natural experiments have often been of a kind or scale that would be otherwise impossible or unethical to implement, their analysis has in several cases suggested important intervention opportunities. In the final section, I discuss the implications of the Malawi famine natural experiment for the conception of HIV prevention and that of related health conditions.