Erythropoietin (EPO) has been proposed to play a central role in the ventilatory acclimatization to continuous hypoxia. The aim of this study was to investigate the effect of training in conditions of normoxia and hypoxia on erythropoietin levels and physical performance in elite endurance runners. In this semi-experimental study, 8 male endurance runners of the national team took part in the study. The training program was the same for all the subjects including continuous, interval, aerobic and resistance training. Runners participated in the training from 15 to 18 sessions a week for 11 weeks of living at altitude, training at altitude and at sea level. 1500 m performance test and blood samples in pretest (basal level of normoxia), posttest 1 (pre-hypoxia), posttest 2 (post-hypoxia) and posttest 3 (after sea level) were measured in four times. The results of the pretest (basal level of normoxia), posttest 1 (pre-hypoxia), posttest 2 (post-hypoxia) and posttest 3 (after sea level) in four measurement times showed a significant difference in the EPO and running performance among the measurement times (P=0.001). The results showed that the EPO values decreased from the beginning to the end of the experimental period (P=0.001). Also, the time of 1500 m running significantly reduced (P=0.001). Regarding the results of this study, it seems that training in hypoxia condition can have a positive effect on the improvement of performance of endurance athletes.