Though both glucocorticoid alterations and memory impairments have been noted in posttraumatic stress disorder (PTSD), it is not clear if these phenomena are causally linked. As there is emerging evidence that these domains become further altered in PTSD with increasing age, it is of interest to examine these relationships in an older cohort. Aging (mean age, 62.7+/-8.9; range, 52-81) combat veterans with (n=13) and without (n=17) PTSD received an intravenous bolus of 17.5 mg hydrocortisone (cortisol), a naturally occurring glucocorticoid, or placebo in a randomized, double-blind manner, on two mornings approximately 1-2 weeks apart. Neuropsychological testing to evaluate episodic and working memory performance was performed 75 min later. Cortisol enhanced episodic memory performance in both groups of subjects, but enhanced elements of working memory performance only in the PTSD+ group. The preferential effect of cortisol administration on working memory in PTSD may be related to the superimposition of PTSD and age, as cortisol had impairing effects on this task in a previously studied, younger cohort. The findings suggest that there may be opportunities for developing therapeutic strategies using glucocorticoids in the treatment of aging combat veterans.