To explore the possible robust changes in neuronal activity in dopamine-poor brain regions after an indirect dopamine agonist, methamphetamine, we have investigated its effects on c-fos expression in rat brain using immunocytochemistry of c-Fos. Intraperitoneal injection of methamphetamine (1.6–4.8 mg/kg), but not of saline, induced a widespread nuclear c-Fos-like immunoreactivity in the pyriform cortex and olfactory tubercle with greatest density followed by the II–VI layers of the neocortex, amygdala, hypothalamus, thalamus, nucleus accumbens and striatum. These expression patterns resemble those elicited by amphetamine and suggest that not only the dopamine-rich subcortical regions but also the cerebral cortex may play a crucial role in behavioral abnormality induced by methamphetamine.