Several studies using animal models have revealed an inverse relation between gluco-corticoid levels and hippocampus volumes. This inverse relation has been interpreted as reflecting the role of the hippocampus in modulating glucocorticoid secretion, as well as the effect of glucocorticoids on the hippocampus. The objective of this study was to examine the relation between hippocampus volumes and baseline and post-challenge salivary cortisol levels in healthy young adults. A double-blind, placebo controlled design was used in which 14 males between 18 and 30 years of age received either 100 mg hydrocortisone or placebo on separate occasions approximately 1 week apart. Baseline and post-challenge cortisol levels were assessed prior to and after magnetic resonance imaging. Volumetric analyses of the hippocampus revealed no differences between the hydrocortisone and placebo conditions; however, post-challenge cortisol levels were inversely associated with total and right hippocampus volumes. Cortisol levels were not associated with the volume of the hippocampus in the placebo condition (i.e. under baseline conditions). The present findings are consistent with other evidence that the hippocampus, as reflected in volume, partially determines the efficacy of negative feedback in modulating cortisol levels.