Background: CD44, the transmembrane adhesion molecule, is expressed in the fetal brain and supposed to mediate neuroglial interactions. We evaluated the expression and distribution of CD44 in the developing human retina. Methods: Four developing human eyes were evaluated at 6, 10, 16, and 21 weeks of gestation, as well as the eyes of one infant and four adults. Frozen sections were immunohistochemically stained with monoclonal antibodies to three human CD44 clones (BU52, F10-44-2, and DF1485) and to vimentin, and antiserum to glial fibrillary acidic protein (GFAP). Specimens were evaluated by light and electron microscopy. Results: Positive immunostaining for CD44 was first detected at 21 weeks of gestation in the longitudinal fibers that extended from the inner to the outer limiting membrane and around capillary vessels with the simultaneous expression of vimentin and GFAP. Immunoelectron microscopy demonstrated the presence of CD44 on the surface of Muller cells and astrocytes. CD44 was faintly seen in the Muller cells in the periphery and definitely present in the astrocytes in the infant and adult retinas Conclusion: CD44 was expressed in Muller cells at a late stage of fetal development and in the fetal, infant, and adult astrocytes, which suggests that it is important in the morphogenesis and homeostasis of the neural retina.