The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on pituitary-adrenal axis responses to stress in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the influence of rHuEPO treatment on corticotropin (ACTH) levels and cortisol responses to insulin-induced hypoglycemia in CAPD patients. Nine clinically stable and well-nourished patients (age 19-59 years) treated with subcutaneous rHuEPO, 34-208 U/kg BW/week, during 6-25 months were studied. Nine patients matched for age, sex, and duration of CAPD and not previously treated with rHuEPO were studied as the control group. Crystalline insulin (0.1 U/kg BW) was injected IV to the fasting subjects. Blood samples were collected before and 15, 30, 60, 90, and 120 minutes after insulin administration. In all blood samples serum cortisol and glucose concentrations were assessed. There were no statistically significant differences between both groups in hematocrit values and blood hemoglobin concentrations. Insulin administration induced a decrease in glucose levels that reached a nadir at 30 minutes in both groups (1.8 +/- 0.1 mmol/L in the rHuEPO group vs 2.1 +/- 0.2 mmol/L in the control group). After hypoglycemic stimuli cortisol levels clearly rose in rHuEPO-treated patients reaching a peak of 720 +/- 71 nmol/L at 60 minutes. However, in the control group the cortisol peak, which was not different from that observed in the rHuEPO group (676 +/- 44 nmol/L), occurred at 90 minutes. The areas under the secretory curve of cortisol did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)