The neurotoxic effects of methamphetamine (MA) on dopaminergic and serotonergic terminals have been well-documented. Another neurotoxic effect of MA is neuronal degeneration in the somatosensory cortex, as seen by silver staining. The neurochemical characteristics of these degenerating neurons are unknown. Using glutamate and glial fibrillary acid protein (GFAP) immunohistochemistry, it was found that MA exposure in adult rats (10 mg/kg given 4 times intraperotoneally (i.p.) at 2-h intervals) causes localized depletion of glutamate-positive neurons and astrogliosis in the somatosensory cortex 3 days following treatment. The affected region covered the middle one-third portion from the longitudinal fissure to the rhinal sulcus and was predominately seen in layers II-III of the cortex. This pattern of depletion is consistent with that demonstrated previously with silver staining following MA, d-amphetamine, and 3,4-methylenedioxymethamphetmine (MDMA) exposures. Comparable efforts were not found in developing animals at ages previously shown to also be resistant to MA-induced effects on dopaminergic terminals (age 20 and 40 days). Results suggest that MA exposure induces degeneration of glutamatergic neurons in the somatosensory cortex of adult rats.