OBJECTIVE Neonatal exposure to psychostimulants is known to produce morphologic alterations in the developing visual system of rats. This study was designed to evaluate the extent of retinal astrocytic response by using the astrocyte localized protein, glial fibrillary acidic protein, after neonatal exposure to cocaine and amphetamine. METHODS Male Wistar rats were given 15 mg/kg body weight/day of cocaine hydrochloride, subcutaneously, from postnatal days 0 to 6, 13, and 29 and were killed at postnatal days 7, 14, and 30; other rats received 10 mg/kg body weight/day of d-amphetamine sulfate following the same protocols. Control rats were given saline or were not manipulated. After transcardiac perfusion with 4% paraformaldehyde whole mounts of flat retinas were processed for glial fibrillary acidic protein immunohistochemistry. Retinas displaying lesions from the amphetamine groups were processed for electron microscopy; vertical semithin and ultrathin sections were observed. RESULTS In cocaine-treated rats extensive sheets of proliferating astrocytes presenting a preferential peripheral localization could be identified. In the amphetamine-exposed rats an enhanced expression of glial fibrillary acidic protein was detected in widespread "loci" of astrocytes observed throughout the whole retinal surface; at postnatal day 30 sheets of proliferating astrocytes could also be identified. CONCLUSIONS Exposure to psychostimulants during active development induced different types of astrocytic responses in the retina, which, as an end result, can lead to functional changes due to the disruption of the retina structural organization.