To evaluate the usefulness of the plasma dehydroepiandrosterone (DHEA)-to-cortisol ratio (D/C) and the plasma aldosterone-to-plasma renin activity ratio (ALDO/PRA) as indicators of stress, we first monitored changes in these ratios associated with surgery in 13 patients who were healthy except for their localized gynecologic diseases. D/C and ALDO/PRA ratios were reduced by 37 and 42%, respectively, 4-5 days postsurgery compared to those 3-4 days before surgery (P less than 0.05 and P less than 0.01, respectively) and returned to preoperative levels 11-13 days after surgery. In contrast, individual hormone levels showed no significant changes associated with surgery. Having documented that these ratios may serve as indicators of stress, we then sequentially measured D/C ratios in patients with gynecologic malignancy subjected to cytotoxic chemotherapy or radiation therapy and in patients in the terminal stage. Although such therapies did not affect D/C ratios to a measurable extent, patients in the terminal stage gave consistently low D/C ratios in spite of normal vital signs (a D/C ratio below 6 was deemed low). Such low ratios occurred only sporadically in other patients and, again, individual values for DHEA and cortisol showed no consistent pattern. We believe that use of D/C ratios as an indicator of stress warrants further investigation.