Development of multiple organ failure is the most complex problem in critically ill patients, and is associated with a high mortality. Asymmetrical dimethylarginine (ADMA) is an endogenously produced inhibitor of nitric oxide synthase, of which the clinical importance is currently being revealed. In Nijveldt et al. (The liver is an important organ in the metabolism of asymmetrical dimethylargenine (ADMA) Clin Nutr 2003; 22: 17-22) we showed that plasma ADMA concentration is elevated in critically ill patients and significantly related to hepatic function. Moreover, plasma ADMA concentration emerged as a strong and independent risk factor for ICU mortality in these patients. Here, we hypothesize that accumulation of ADMA is a causative factor in the development of multiple organ failure by interfering with important physiological functions of nitric oxide production.