Expression of the immediate early gene c-fos is increased in mammalian neurons by a number of stimuli and the usefulness of this gene as a marker of neuronal activation has been demonstrated in several systems. Directly-acting dopamine agonists of the D1-type (SKF 38393, CY 208-243) and indirectly-acting dopamine agonists (amphetamine, cocaine) all produce a rapid and transient increase in Fos protein levels in varying patterns in striatum and cerebral cortex. Directly-acting dopamine agonists only produce c-fos activation in denervated (supersensitive) striatum whereas cocaine and amphetamine activate c-fos in striatum in naive animals. Remarkably, D2 selective antagonists such as haloperidol, albeit in high doses, also activate c-fos expression. Activation of c-fos and other immediate early genes may play a part in the development of such long-term dopamine-related effects as dyskinetic movements and addiction.