A reference range for fetal mean red cell volume (MCV) with gestation was established from the study of samples obtained by cordocentesis from 466 pregnancies undergoing prenatal diagnosis for non-erythrocyte abnormalities. The mean MCV decreased from 145 fl at 16 weeks to 113 fl at 36 weeks of gestation. Alterations in MCV were investigated in 154 red cell isoimmunized and 231 small for gestational age (SGA) fetuses. In red cell isoimmunization, significant macrocytosis was observed when the fetal hemoglobin concentration deficit was ≥6 g/dl. In the chromosomally normal SGA fetuses (n = 178), the MCV was increased and the magnitude of macrocytosis was significantly associated with gestation and the degrees of fetal ‘smallness’ and fetal hypoxemia. However, the most severely macrocytotic SGA fetuses were those with triploidy (n = 22). In the SGA fetuses with other chromosomal defects (n = 31), the MCV was higher than the controls but lower than that of the chromosomally normal hypoxemic fetuses. It is suggested that in severe growth retardation there is developmental delay in the normal evolution from hepatic to medullary hemopoiesis and this is most marked in triploid fetuses. In contrast, in red cell isoimmunization the switch to medullary erythropoiesis is normal, but in severe anemia there is secondary recruitment of hepatic erythropoiesis.