We have recently described a two-step liquid culture system that supports the proliferation and maturation of human erythroid progenitors. Several days after the addition of erythropoietin, the cultures undergo erythroid differentiation in a synchronized fashion. The purpose of the present study was to determine detailed kinetics of globin gene expression at the mRNA level in adult and newborn erythroid cells. Our results show that in cultures derived from normal adult peripheral blood, the mRNA levels of alpha- and beta-globin genes increased throughout most of the culture period, whereas gamma-globin mRNA remained at a low level. In contrast, high expression of all three globin genes, alpha, beta, and gamma, was observed in cultures derived from cord blood. The results demonstrate that the populations of erythroid progenitors in cord blood and in adult peripheral blood are fundamentally different, suggesting that this culture system recapitulates the normal pattern of globin gene expression, providing a valuable tool in the investigation of the regulation of the switch from fetal to adult hemoglobin.