It was previously demonstrated that the 90 kDa cell adhesion molecule CD44 is localized to Müller cell apical microvilli which project into the interphotoreceptor matrix in the adult retina. For the current report, the distribution of CD44 was studied in developing normal BALB/c mouse retinas and in rds mutant mouse retinas of various ages. Using immunoperoxidase techniques, positive label for CD44 was first detected on Müller cell microvilli after 7 days postnatal in BALB/c retinas and the band of label widened as the microvilli elongated and the retina reached maturity. Labeling of the radiating Müller cell bodies within the retina was also observed during development, and this distribution of CD44 is most likely related to retinal cell differentiation and maturation which are taking place at this time. This label was not observed in mature retinas. In the rds mouse retina, a normal labeling pattern for CD44 was observed on Müller cell microvilli at early ages, prior to photoreceptor degeneration. During the time course of the degeneration, microvillar labeling was still seen, however labeling of the radiating Müller cell bodies within the retina increased dramatically. Following degeneration, the Müller cell microvilli appeared to have retracted or collapsed and the inner retinal labeling was not observed. Only a residual label remained at the level of the outer limiting membrane. The increased presence of CD44 within the rds retina during photoreceptor degeneration is likely due to an upregulation of CD44 synthesis by the Müller cells and/or to the transfer of CD44 from retracting microvilli into lower portions of the Müller cells.