Background, material and methods: This study was performed in 20 patients with end-stage chronic renal failure (CRF) and 10 healthy volunteers, All of the patients were on regular hemodialysis treatment (RHD), 10 of whom were on recombinant human erythropoietin (rHuEPO) therapy. Hematocrit levels of the patients with CRF on rHuEPO were between 0.30 to 0.33 and not on rHuEPO were below 0.24. Baseline serum T-3, T-4, fr(3), fT(4) and TSH levels were measured and TRH stimulation test was performed in patients and control subjects. Serum TSH levels were measured hourly during the afternoon (2 to 5 p.m.) and at night (10 p.m. to 2 a.m.) to determine the nocturnal rhythm of TSH. Results: The mean T3 in rHuEPO, not rHuEPO and control groups were 98.01 +/- 5.54, 70.55 +/- 7.09, 98.29 +/- 4.2 ng/dl; T-4 6.47 +/- 0.68, 6.39 +/- 0.59, 8.35 +/- 0.46 ng/dl; fT(3) 2.24 +/- 0.19, 1.52 +/- 0.24, 2.29 +/- 0.17pg/ml and fT(4) 0.88 +/- 0.14, 0.75 +/- 0.14, 0.97 +/- 0.10 ng/dl, respectively. These values were significantly lower in patients not on rHuEPO compared to controls (p < 0.05). In patients on rHuEPO only T4 values were lower than in the controls (p < 0.05). In patients not on rHuEPO the T3, and fr3 were significantly lower than the values of patients on rHuEPO treatment (p < 0.05). Normal in 8 (80%), blunted in 1 (10%), no TSH response in I (10%) to TRH stimulation were obtained in rHuEPO group. TSH response was normal in 1 (10%), and delayed in 9 (90%) patients not on rHuEPO. The circadian nocturnal rhythm of TSH was abnormal in 8 (90%) patients not on rHuEPO, in 2 (20%) patients on rHuEPO. As a result, CRF and RHD distorts the circadian TSH rhythm and substantially change the thyroid hormone profile probably by affecting hypothalamic-pituitary-thyroid axis. Distortion of the circadian rhythm of TSH and TSH response to TRH points to a defect at the level of hypothalamus and pituitary gland. Conclusion: rHuEPO treatment has some beneficial effects on hypothalamo-pituitary-thyroid axis in the patients on RHD.