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Objective: In previous studies of ovine fetuses, plasma erythropoietin (EPO) concentration increased 10- to 20-fold at 24 hours after hemorrhage and returned toward normal at 48 hours. The present study in fetal sheep was designed to determine in detail the time course of the hemorrhage-induced changes in plasma EPO levels and explore the relationships among EPO concentration, blood oxygen tension, and hematocrit.Methods: Chronically catheterized, late gestation ovine fetuses (n = 12) were hemorrhaged such that 40% of their blood volume was lost over 2 hours. Plasma EPO concentration, arterial blood gases, pH, and hematocrit were determined at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, and 36 hours after initiating the hemorrhage. Plasma EPO concentration was determined by radioimmunoassay. Statistical analyses included analysis of variance and least squares regression.Results: Mean plasma EPO concentration increased significantly (2.3 ± 0.5 [± standard error of the mean] times basal values) at 4 hours after initiating the hemorrhage, reached a maximum (33.8 ± 12.9 times basal values) at 10–16 hours, and decreased to 50% of maximal values at 24 hours after hemorrhage. Hematocrit decreased rapidly during the 12 hours after hemorrhage (P < .0001), whereas arterial blood oxygen tension remained unchanged. The logarithm of EPO concentration was correlated with hematocrit (r = −0.74, P < .0001) but not with arterial blood oxygen tension.Conclusions: Blood EPO concentration began to increase at approximately 3–4 hours after the onset of hemorrhage. Further, EPO concentrations at 24 hours after hemorrhage represented only 50% of the maximal EPO response. The correlation between EPO and hematocrit suggests that blood oxygen content rather than oxygen tension is the more important stimulant for augmented EPO production after fetal hemorrhage. [Copyright &y& Elsevier]