Several alterations in growth hormone (GH) secretion have been reported in patients with chronic renal failure. The aim of the present report has been to assess the effect of acutely administered recombinant human erythropoietin (rHuEPO) infusion on GH responses to thyrotropin-releasing hormone (TRH) in uremic patients. Twelve male patients (mean age 46.2 years, range 24 to 69) were studied. Seven of them were on continuous ambulatory peritoneal dialysis (CAPD), two on chronic hemodialysis (HD) and two in pre-dialysis (PreD). None had been treated before with rHuEPO. Each patient was tested with TRH (400 micrograms i.v. in bolus), and with TRH plus rHuEPO (40 U/kg in constant infusion for 30 min) on different days. TRH administration provoked a paradoxical response of GH (peak > 5 micrograms/liter) in nine (5 CAPD, 2 HD, 2 PreD) out of 12 patients. In this group of patients with anomalous GH responses, rHuEPO infusion produced an abolishment of the paradoxical responses (GH peak < 5 micrograms/liter) in eight patients and a marked decrease in a further one. On the contrary, in patients with no paradoxical GH response, stimulation with TRH plus rHuEPO did not induce any change in GH release compared with that observed after TRH alone. rHuEPO had no effect on TRH-induced thyrotropin release. These results suggest that the paradoxical GH response to TRH in patients with chronic renal failure is blocked by rHuEPO administration. This rHuEPO action might be mediated by an increased release of somatostatin or an inhibited GH-releasing hormone secretion.