To study the diurnal rhythm of plasma cortisol and corticosteroid binding-globulin (CBG) in brain-injured patients managed in an intensive care unit (ICU). Observational clinical study. Twelve-bed medical/surgical critical care facility. Fifteen acute brain-injured (coma-inducing) patients: nine following trauma and six with subarachnoid haemorrhage (SAH). One morning and one evening blood sample were obtained from each patient via an existing arterial line at times which coincided with clinically indicated blood tests. The total cortisol measurements in this sample of brain-injured patients is similar to the normal reference range. Only two patients had morning total cortisol measurements greater than the reference range, 140-690 nmol/l, and five patients had evening measurements greater than the 80-330 nmol/l reference range. Eight patients demonstrated diurnal variation of plasma cortisol. Plasma CBG was significantly decreased in all 15 brain-injured patients. All patients had a free cortisol percentage greater than the quoted reference of 5% and five patients had measurements between 12-23%. No diurnal variation in CBG was detected. There was no association between age or mode of injury and cortisol secretion. Following acute severe brain injury, total serum cortisol is not elevated. This may indicate 'relative' hypocortisolaemia in relation to the clinically assessed stress. However, because of the decline in plasma CBG, plasma free cortisol is increased after acute severe brain injury.