The effects of exogenous gangliosides on sprouting of optic tract axons was studied in hamsters which, after a right tectal lesion on the day after birth (P1), had an abnormal retinotectal projection from the left eye to the left superior colliculus (SC). Sprouting of these axons was induced by removing the competing input by right eye removal on postnatal day 9 (P9). Intraperitoneal GM1, given daily and started on P9, significantly stimulated the sprouting response. This was demonstrated by Fink-Heimer silver staining of anterograde axonal degeneration three days after the left eye was removed on P36. Terminal fields in the left SC were, in average, twice as large compared to controls. An estimate of the total number of terminals (silver stained particles) revealed a value of 7.9 X 10(6) for GM1 and 3.2 X 10(6) for control hamsters, respectively. Diencephalic structures which also receive collateral input from the sprouting optic tract did not show any alterations in the size of the terminal field due to GM1-treatment, suggesting that, in vivo, gangliosides fail to initiate sprouting in areas that have not previously been denervated. Unexpectedly, GM1-treated hamsters also had significantly smaller right SC damage and less left damage near the midline. Subsequent reanalysis of the data based on a lesion-matching procedure indicates that effects on reducing atrophy were independent of the GM1-enhanced sprouting of retinofugal axons. These findings provide the first direct evidence that exogenous GM1 stimulates lesion-induced axon sprouting in the mammalian brain.