["Acta Physiologica, Volume 232, Issue 3, July 2021. ", "\nAbstract\n\nAims\nTotal haemoglobin mass (tot‐Hb) increases during high‐altitude acclimatization. Normalization of tot‐Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m).\n\n\nMethods\nNewly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19‐day high‐altitude sojourn by ingestion of 13C2‐ and 15N‐labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot‐Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling.\n\n\nResults\nTot‐Hb increased by 4.7% ± 2.7% at high altitude and returned to pre‐altitude values within 11 days after descent. Elimination of 13C‐ (normoxia) and 15N‐ (high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71‐positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3‐4 days after descent and normalized slowly. There was no indication of haemolysis.\n\n\nConclusion\nWe confirm a rapid normalization of tot‐Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes.\n\n"]