ObjectiveTo investigate the possibility of early changes in erythropoiesis during prolonged exercise being reflected in reticulocyte parameters.DesignThis was a case-control field study of hematological variables in a group of ultramarathon runners competing in a 6-day track race.SettingA 6-day ultramarathon in Colac, Australia.Participants7 male and 1 female experienced ultramarathon runners.InterventionA track race of 6 days' duration.Main Outcome MeasuresA wide range of red cell and reticulocyte parameters.ResultsResting red cell parameters were within normal clinical limits. However, except for the expected findings typical of hemodilution, red cell parameters were relatively unchanged during and after the event, with the exception of small but statistically significant changes in number and percentage of macrocytic, microcytic, hypochromic, and hyperchromic red cells. No reticulocytosis was found in an event that would have been expected to be associated with significant foot-strike hemolysis; however, an increase in the percentage of reticulocytes with high RNA content late in the event indicates early release from the marrow. Reduction in reticulocyte mean cell volume, which is consistent with functional iron deficiency, was demonstrated during the event. This finding is consistent with changes in some of the iron-related parameters associated with the acute phase response, but the dissociation in time between these changes makes a causal relationship unlikely. Other changes such as those in reticulocyte hemoglobin distribution width, reticulocyte distribution width, cell hemoglobin concentration mean, and lack of change in corpuscular hemoglobin are not typical of true iron deficiency, and the mechanism of these changes is currently unknown.ConclusionThe hematopoietic system demonstrates remarkable stability in the face of very significant exercise stress. No reticulocyte response was demonstrated in this study, but reticulocyte changes both consistent with and contrary to early release from the marrow were demonstrated after several days of strenuous running. The significance of several newly developed ratios of red cell and reticulocyte parameters in conditions of exercise stress requires further investigation.