Marie-Pierre Moisan massive amounts of cortisol at sites of inflammation by virtue of its SERPIN structure. Additionally, our studies in CBG deficient mice demonstrate that the pres ence of CBG is necessary to mount a normal stress response. 6–7 Contrary to what one might have expected, CBG deficiency leads to signs of hypocortisolism rather than hypercortisolism: free cortisol and cortico sterone levels are normal under resting con ditions and suboptimal after stress. Thus, the main, and perhaps sole, function of CBG seems to be the retention in blood of a circulating gluco corticoid reserve readily available in case of an emergency. Perogamvros et al. report the necessity of measuring free rather than total cor tisol levels to assess HPA axis function in patients. Although this approach would be progress, knowledge of free cortisol levels does not answer the question of whether cortisol exerts its actions normally or not. Indeed, free cortisol levels could be ele vated, but if its receptors are desensitized cortisol action will not be effective. Cortisol acts on cells by binding to specific receptors that are transcription factors modulating the expression of target genes. These target genes have either glucocorticoid response elements in their promoter sequence or other DNA motifs for interfering transcrip tion factors, such as NFκB. These proper ties are used in transcriptomic analyses, in which the level of global gene expression is examined followed by the use of promoter sequencebased bioinformatic tools to iden tify glucocorticoid targets. 8 This approach for assessing HPA axis function has been used successfully in stress research, 9–10 requires a single 5 ml blood collection and its cost is reducing.