Single-stranded RNA viruses from four different families cause a syndrome of fever and malaise, 'capillary leak' with loss of plasma volume, and coagulation defects which can lead to bleeding. Although direct cytopathic effects can contribute to disease severity, most features of illness are caused by innate immune responses, as the systemic spread of virus to macrophages and dendritic cells leads to the release of mediators that modify vascular function and have procoagulant activity. The synthesis of tissue factor by infected cells can also trigger coagulation. Failure of adaptive immunity through impaired dendritic cell function and lymphocyte apoptosis can have a crucial role in fatal infection.