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Nitric oxide (NO) is an important mediator of host defence and of vascular tone. In septic shock, upregulation of inducible NO synthase leads to the production of vast amounts of NO, which contribute to pathogen elimination but also to inappropriate vaso-dilation and to loss of vascular resistance. Asymmetric dimethyl-arginine (ADMA) is an endogenous inhibitor of NO synthases shown to contribute to the regulation of vascular tone. ADMA was recently identified as a marker of organ dysfunction and mortality in intensive care patients and as a novel cardiovascular risk factor. In the present issue of Critical Care, a study by O'Dwyer and colleagues identifies ADMA as a potential regulator of NO production in septic shock. Being an inhibitor of NO production, ADMA may at least partly counteract pathological hypotension, but at the same time may impair the NO-dependent host defence. A mechanism is proposed by which the interplay between ADMA and inducible NO synthase activity is mediated. ADMA levels should be determined in future studies evaluating the regulation of NO in the intensive care setting. In the present issue of Critical Care, O'Dwyer and colleagues [1] report the results of a study in 47 patients with septic shock. Asymmetric dimethylarginine (ADMA) levels were elevated in these patients at the time of admission to the intensive care unit (ICU) as compared with a group of 10 healthy controls. ADMA levels in septic patients directly correlated with the Sequential Organ Failure Assessment scores, with the degree of acidaemia and lactaemia, and with vasopressor requirements. Interestingly enough, ADMA levels were higher in patients requiring vasoactive infusions than in those not requiring vasoactive infusions. ADMA levels further increased during the subsequent 7 days of ICU treatment. Nonsurvivors tended to have higher ADMA plasma levels on days 1 and 7 of ICU treatment as compared with survivors, although this trend was insignificant in the small patient group. The authors also demonstrated that a genetic polymorphism in the promoter region of the dimethylarginine dimethylaminohydrolase (DDAH) II gene was significantly associated with ADMA levels in these patients, suggesting that the genetically anchored dysfunction of the enzyme that metabolises ADMA may importantly regulate ADMA levels. Standard therapy for patients with sepsis includes ICU admission, careful selection of antibiotic therapy, and, if needed, haemodynamic and ventilatory support [2]. Despite the use of these intensive therapies, however, mortality from sepsis has remained at levels between 35% and 50% [2]. Nitric oxide …