Objective: Treatment of anemia with recombinant human erythropoietin (rHuEpo) in hemodialysis patients has been associated with improvement of several abnormalities in hypothalamic-pituitary function. The aim of the present study is to investigate the effects of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid hormone axis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Design: Single center, prospective study. Patients and methods: Ten patients who were clinically stable and had been on CAPD were evaluated. Eleven age and sex matched healthy volunteers were chosen as controls. All of the patients were clinically euthyroid. All patients were on CAPD therapy and none of them had received rHuEpo treatment previously. In all patients after basal estimations of free T-3, free T-4, TSH, GH and prolactin levels, a bolus of 400 mug TRH was administered intravenously. Levels of TSH, GH and prolactin were measured in blood samples collected every 30 min of the 3 h test period. After the treatment with rHuEpo, TRH test with the same protocol was repeated. Results: Before the improvement in serum hemoglobin levels with rHuEpo treatment, the patients on CAPD showed abnormal hypothalamic-pituitary-thyroidal functions, including delayed and prolonged TSH (NS), paradoxically elevated GH (p < 0.001) and increased and prolonged prolactin (p = 0.001) responses to TRH. After improvement of anemia with rHuEpo no significant difference was found between the patients and control groups for baseline TSH levels. In the patients peak TSH level and AUC of TSH secretion were significantly reduced after the treatment (p < 0.05 for both). Furthermore the improvement in anemia did not eliminate the paradoxic GH and prolonged prolactin responses to TRH administration. Conclusion: Some hypothalamic-pituitary-thyroid function abnormalities including delayed and blunted TSH, increased and prolonged prolactin and paradoxical GH responses to TRH administration were observed in uremic patients treated with CAPD and the improvement in anemia with rHuEpo seems to cause slight changes on the hypothalamic-pituitary-thyroid axis and peripheral thyroid hormones.