Intercellular adhesion molecule 1 (ICAM-1) mediates the binding of Plasmodium falciparum to vascular endothelium. In a case-control study of falciparum malaria in Gambian children, we have looked for evidence that a generalized increase in expression of ICAM-1 is associated with cerebral malaria. Plasma levels of circulating ICAM-1 (cICAM-1) were significantly higher in 246 children with acute malaria than in 156 children with non-malarial illnesses. cICAM-1 levels correlated with levels of tumour necrosis factor (TNF), interleukin 1 alpha (IL-1 alpha) and interferon gamma, supporting the view that these cytokines are responsible for a general upregulation of ICAM-1 expression in malaria. However, while it has been previously shown that TNF and IL-1 alpha levels were related to disease severity, this was not the case for cICAM-1. It may be that differences in the distribution of ICAM-1, rather than its total level of expression, are critical in determining the clinical outcome in malaria.