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.