Ibogaine causes degeneration of Purkinje cells (PKCs), presumably via activation of neurons in the inferior olive leading to release of glutamate at climbing fiber terminals. Following ibogaine administration, some Purkinje cells express NADPH-diaphorase and neuronal NOS (nNOS), neither of which is present normally in these cells. The induction of NOS is delayed in onset, dose-related, and detected in neurons adjacent to degenerated PKCs. The results demonstrate that nNOS induction can follow excitotoxic neuronal injury or perturbation. However, NO is unlikely to participate in the initial phase of PKC damage. Both the late induction of nNOS and the spatial relationship between damaged and nNOS-expressing PKCs are consistent with a role for NO in either neuronal recovery or delayed cell death following excitotoxic injury.