BACKGROUND In patients with chronic renal failure, rHuEpo therapy ameliorates anaemia and improves wellbeing, exercise tolerance, and appetite. Both leptin and neuropeptide Y play an important role in regulation of appetite and energy balance in humans. METHODS The present study aimed to assess the influence of 12 months rHuEpo therapy on plasma leptin and neuropeptide Y concentrations in 15 haemodialysed patients (HDP) (6F, 9M; mean age 40.8+/-2.9 years; mean BMI 23.6+/-1.1 kg/m2; mean duration of HD 3.3+/-0.6 months) (Epo group). A second group (No-Epo group) consisted of 17 HDP (9F, 8M; mean age 44+/-3.2 years; mean BMI 24.3+/-1.0 kg/m2; mean duration of HD 2.5+/-0.4 months) not treated with rHuEpo for 12 months. Basal plasma leptin and neuropeptide Y concentrations were estimated by RIA at the beginning and after 3, 6, 9 and 12 months of rHuEpo therapy (Epo group) or clinical observation (No-Epo group). The control group consisted of 30 healthy subjects (15 females, 15 males, mean age=38.2+/-1.7 years, mean BMI 24.5+/-0.7 kg/m2). RESULTS Baseline plasma leptin concentrations in HDP were higher, although statistically not significant than leptinaemia in healthy subjects. After 3, 6, and 12 months of rHuEpo therapy plasma leptin concentrations were significantly lower than at the beginning of the study. Baseline plasma neuropeptide Y concentrations in HDP did not differ significantly from controls. After 3 and 6 months of the study period plasma neuropeptide Y concentrations increased significantly in patients of both the Epo and No-Epo group. This increase was, however, significantly higher in rHuEpo-treated than in untreated patients. CONCLUSIONS (1) rHuEpo treatment in haemodialysed patients with chronic renal failure is followed by a significant decline of leptinaemia and disappearance of the physiological positive BMI/leptinaemia relationship. (2) Suppression of leptinaemia induced by rHuEpo may be of clinical relevance in haemodialysed patients with chronic renal failure.