Research linking post-traumatic stress disorder (PTSD) to hypercortisolism in laboratory experiments was extended to a natural clinical setting. Mothers of children diagnosed with a life-threatening illness (N=92) completed standardized measures of PTSD and provided a salivary cortisol sample during their child's medical check-up (Time 1) and again 24. h later, after the threat of possible negative medical reports was removed (Time 2). Women who met diagnostic criteria for PTSD exhibited significantly higher cortisol levels at Time 1 compared to women who did not meet criteria for a diagnosis. No significant differences were observed for cortisol levels at Time 2 between the women with and without PTSD. These findings extend current laboratory findings linking hypercortisolism and PTSD to a natural, stressful situation. Implications for understanding the etiology of PTSD as well as for possible prevention and intervention options are discussed. © 2011 Elsevier Ltd.