Exogenous gangliosides have been reported to enhance neurite formation in vitro and in vivo after damage to peripheral nerves. We report here the effects of ganglioside treatment on the course of recovery of alternation behavior that follows a unilateral lesion of the rat entorhinal cortex. The recovery of this function is known to parallel rapid synaptic reinnervation (collateral sprouting) into the partially denervated dentate gyrus of the hippocampus which previously received afferent input from the entorhinal region. Rats trained on an alternation behavior were subjected to a unilateral entorhinal lesion and subsequently given daily injections of total ganglioside (50 mg/kg, i.m.). Testing of the behavior continued for 2 weeks to assess the extent of behavioral impairment and the rate of recovery. Rats treated with gangliosides showed reduced behavioral impairment, accelerated recovery of the learned behavior, and final performance levels greater than controls. We hypothesize that the gangliosides may be interacting with regenerating neuronal membranes, either acting as receptors for trophic growth factors or altering membrane structure itself.