Adrenalectomy protects hippocampal pyramidal cells from transient ischemia in rats. We hypothesized that this effect of adrenalectomy could be generalized to the gerbil. We determined the effect of glucocorticoid manipulation on hippocampal CA1 cell death following transient forebrain ischemia in the gerbil. Adrenalectomy diminished hippocampal damage when performed immediately following transient forebrain ischemia, as in the rat, while glucocorticoid administration resulted in an increase in CA1 pyramidal cell damage. Furthermore adrenalectomy 24 h after the ischemic injury diminished hippocampal damage to roughly the same extent as immediate adrenalectomy. However, if gerbils were examined at longer survival periods after ischemia, the difference in hippocampal damage between adrenalectomized and sham-adrenalectomized was lost. These findings suggest that glucocorticoids influence the rate of hippocampal pyramidal cell disappearance following ischemia. Manipulation of glucocorticoids could be an important adjunct to therapy for preventing ischemic brain damage.