Nucleus basalis magnocellularis (NBM) cholinergic neurons, furnishing the major portion of the extrinsic cholinergic innervation of the rat cortex, undergo specific retrograde changes in cell somata and choline acetyltransferase (ChAT) activity after cortical lesions. These are prevented in young and mature animals, but not in aged rats, by the chronic administration of exogenous ganglioside GM1 after lesioning. However, a delay of 10 days (in young animals) in the commencement of treatment averted the responses to GM1 in lesioned animals. It is suggested that the effects of exogenous gangliosides on retrograde biochemical and morphological alteration of cholinergic neurons may vary with circumstances permissive of plastic changes of central nervous system neurons at the time of administration.