Dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) is an enigmatic and growing public health problem which is confined at present to countries of South-East Asia. Since 1956, over 350 000 patients have been hospitalized and nearly 12 000 deaths have been reported. Dengue viruses, a group of four flaviviruses, are transmitted to man by Aedes aegypti. Currently, dengue viruses are actively transmitted in 61 countries which circle the globe in the tropical zone and have a combined population of 1500 million. Because the precise antecedents to DHF/DSS are unknown, the public health hazard posed by this syndrome is potentially worldwide. Epidemiological studies in South-East Asia clearly link DHF/DSS to individuals who have had a previous dengue infection or who have acquired maternal dengue antibody. Such antibody may serve as an opsonin, enhancing dengue virus infection of mononuclear phagocytes-the type of cell in man to which dengue infection may be confined. Antibody-mediated infection of these cells is the central concept in the hypothesis of immune infection enhancement. This hypothesis provides a conceptual framework for design of future research. There is an urgent need for a comprehensive identification of "risk factors" in DHF/DSS. This research could be approached by undertaking comparative prospective epidemiological studies in dengue-endemic areas with and without DHF/DSS. Although important progress is being made in the development of attenuated dengue vaccines for each dengue type, a clearer understanding of the pathogenesis of DHF/DSS may be required to provide guidelines for safe and lasting immunoprophylaxis in man.