Many adverse effects commonly associated with chemotherapy, such as nausea, vomiting, and fatigue, are also characteristic of adrenal insufficiency. It is conceivable that chemotherapy drugs may directly or indirectly impact the activity of the hypothalamic-pituitary-adrenal axis. We examined this conjecture by characterizing temporal changes in blood cortisol concentrations in women with ovarian carcinoma given chemotherapy. Twenty-three chemotherapy-naïve women with histologically confirmed ovarian cancer underwent serial blood sampling for determination of cortisol levels prior to and every hour for 6 hr following two chemotherapy treatments with cisplatin or carboplatin. Samples were also taken for 4 hr on a comparison day when all study procedures were performed except chemotherapy administration. A significant reduction in serum cortisol was found immediately following infusion of either cisplatin or carboplatin. No progressive reduction in cortisol was found over the two treatment cycles. Because the reduction in cortisol was seen only in the presence of the cytotoxic drug, it is likely that the effect of the drug is “direct” and does not involve overt psychological or circadian mechanisms. The possible role of this reduction in cortisol is discussed in relation to induction of chemotherapy-induced nausea and vomiting.