The temporally protracted heredodegeneration of cerebellar Purkinje cells in shaker mutant rats can be modified: ablation of the inferior olive accelerates their degeneration whereas chronic intraventricular infusion of trophic factors extends their survival. The present study sought to determine if chronic trophic factor infusion could block the accelerated degeneration of Purkinje cells due to inferior olivary chemoablation thereby focusing on possible mechanisms for the amelioration of heredo-Purkinje cell death. When the inferior olive was chemically ablated with 3-acetylpyridine at the midpoint of 2 weeks of conjoint intraventricular infusion of glial cell line-derived trophic factor (GDNF) and insulin like growth factor type I (IGF-1) Purkinje cells were not protected by the exogenous trophic factors, but rather degenerated prematurely consistent with chemoablation alone. These findings support the conclusion that when the inferior olive is ablated, Purkinje cell heredodegeneration progresses through a mechanism not significantly affected by the action of these trophic factors.