BACKGROUND In Royal College of Surgeons (RCS) rats the retinal pigmented epithelium (RPE) exhibits defective phagocytosis of rod outer segments, causing degeneration of the photoreceptor layer. It is not known whether another function of the RPE, ion and fluid transport, is also affected by the disease. One enzyme involved in modulation of RPE transport activities is carbonic anhydrase (CA). To clarify whether changes in CA activity are correlated with the process of retinal degeneration, the localization of CA activity in RCS rat eyes was investigated. METHODS Eyes of 12 RCS rats and 12 age-matched congenic controls of different ages were studied, using a modified histochemical method of Hansson for light and electron microscopy. RESULTS Control eyes showed CA staining in corneal endothelium, both layers of ciliary epithelium, Müller cells, inner segments of photoreceptors, and RPE cells. In RPE the apical membranes were most intensely stained. In RCS rats, changes in CA staining were seen only in the posterior segment of rats 6 and 7 months of age. Most of the RPE cells were more intensely stained than those of age-matched controls, especially due to increased CA activity in the basolateral membrane infoldings. Adjacent endothelial cells of the choriocapillaris and of retinal capillaries developed staining for CA activity. CONCLUSIONS Changes in CA activity in the RPE and adjacent capillary endothelium, together with previously described changes in RPE morphology in RCS rats, indicate changes in ion and fluid transport across the RPE. Since the retina was already impaired when the increase in CA activity occurred, we hypothesize that the causative factor is not the genetic defect per se, but the destruction of the retina.