As already reported short-term rHuEpo treatment influences plasma insulin, glucagon, pancreatic polypeptide (PP), and gastrin secretion in haemodialysed patients. The present study aimed to assess the influence of long-term rHuEpo treatment on secretion of above mentioned hormones. A total of 27 haemodialysed patients and nine healthy subjects were examined. Nine patients with uraemic anaemia were treated with rHuEpo for 12 months (Epo group) while another nine patients did not receive rHuEpo (non-Epo group), but were monitored biochemically and clinically as patients of the Epo group. The third group (HD) comprised nine haemodialysed patients with a haematocrit value of greater-than-or-equal-to 30% without rHuEpo therapy. In all subjects plasma levels of insulin, glucagon, gastrin, and PP were estimated before and after administration of a test meal. Patients of the Epo group were examined before and after 6 and 12 months of rHuEpo treatment (patients of the Epo group) or clinical monitoring (patients of the non-Epo group) respectively, while only one test was performed in patients of the HD group and healthy subjects. Six months of rHuEpo treatment was followed by an increase of fasting insulinaemia and a decrease of basal plasma level of glucagon and PP. At that time point rHuEpo therapy also increased the response of insulin, glucagon, and gastrin to the test meal. After 12 months of rHuEpo therapy basal insulinaemia returned to the pretreatment value while plasma levels of PP and glucagon were still lower than pretreatment ones. After 12 months of rHuEpo therapy the response of PP secretion to a test meal was higher while that of gastrin secretion lower that the pretreatment ones. Our results suggest that rHuEpo treatment exerts a profound effect on secretion of insulin, gastrin, PP, and glucagon secretion, which seems to be dependent upon duration of rHuEpo therapy and not only, or exclusively, to improvement of the haematological status.