Rat transient incomplete forebrain ischemia was induced by 60 min of bilateral carotid artery occlusion associated with systemic hypotension. Intraperitoneal treatment with either GM-1 monosialoganglioside or its inner ester AGF-2 started 1 h after release of carotid clamps and was repeated twice a day. Ganglioside treatment was effective in reducing the increase of cerebral water content, nonetheless AGF-2 reduces significantly not only cerebral edema, but also potassium efflux and calcium overload. With respect to ischemic untreated rats, GM-1- and AGF-2-treated rats showed a higher incidence of conditioned response retention of a single training trial, associated with improvement in cerebral blood flow and electrocorticographic patterns. In addition, 4 weeks following ischemia, the extent of tissue necrosis was reduced, although not statistically significant, in both ganglioside-treated groups. However, all these improvements are more evident in the AGF-2-treated rats than in the GM-1-treated ones. In conclusion, these results suggest that, except in some cases with different potency, both monosialoganglioside GM-1 and its inner ester derivative, AGF-2, are able to improve outcome after brain ischemia.