Neuronal cell death in hippocampal remnants was seen after methamphetamine (METH) exposure. Two techniques (Fluoro-Jade labeling and argyrophylia) showed that neuronal degeneration occurred in the indusium griseum, tenia tecta and fasciola cinerea within 5 days post-METH exposure in 70% of the mice. Neurodegeneration also occasionally occurred in the piriform cortex, hippocampus and frontal/parietal cortex. This cell death, unlike striatal neurotoxicity, was not dependent on magnitude of hyperthermia occurring but did correlate with behavioral seizure activity during METH exposure. Excitotoxic mechanisms may be underlying the neuronal degeneration since co-administration of phenobarbital blocked cell death.