Interleukin-18 (IL-18) is a potent proinflammatory cytokine that induces interferon-gamma (IFN-gamma) production from Th1 cells, NK cells and activated macrophages, particularly in the presence of IL-12. However, it is also shown that without help from IL-12, IL-18 is capable of inducing IL-4 and IL-13 production in T cells, NK cells, mast cells and basophils, and that administration of IL-18 in conjunction with an allergen increases serum IgE levels. In order to clarify the role of IL-18 in disease severity of falciparum malaria, we have examined serum levels of IL-18, IFN-gamma, and IgE for 96 patients with falciparum malaria [Trans. R. Soc. Trop. Med. Hyg. 97, 236-241]. Results suggested that IL-18 plays a key role in inducing severe malaria through a pathway of elevating IFN-gamma, rather than its IgE inducing activity. Based on these results, the role of IL-18 in severe falciparum malaria will be discussed in this review.