During induced differentiation and maturation of HD3 cells (a chicken erythroblast cell line infected with a temperature-sensitive mutant of the avian erythroblastosis virus), the levels of transferrin receptor (TFR) and nucleoside transporter increase. Both these activities increase before elevated levels of hemoglobin are detected. Shortly after induction, as cellular TFR levels rise, a native-size TFR is detected in the cell-free culture medium, associated with an exosome fraction (100,000 xg pellet). Nucleoside transporter (measured as NBMPR-binding activity) is not increased in this pellet with induction. Previous studies have suggested that exosome formation in peripheral reticulocytes may be a significant route for loss of specific membrane proteins (Johnstone et al., 1991). Although the present experiments in HD3 cells do not address the quantitative importance of exosome formation, the studies suggest that exosome formation is an early event in commitment to the red cell lineage and is not a phenomenon restricted to the terminal stages of red cell maturation.