Tremendous progress has been achieved in developmental, cellular and molecular immunology in the past 20 years, largely due to studies using the mouse as a model system and the arrival of molecular genetics. Immunology is now faced with a difficult challenge. What are the functions of the individual cells and molecules in achieving immunity to infection? Renewed interest in animal models of disease has provided considerable insight in this area, but such models of infection suffer from the inherent limitation of being experimental. In humans, the complex host–environment interaction occurs in natural, as opposed to experimental, conditions. The human model is therefore an indispensable complement to animal models, as it allows an observational genetic dissection of immunity to infection.