Cocaine, a catecholamine agonist, has been shown to produce a transient induction of the immediate-early gene c-fos and its protein product Fos in the striatum of normal rats. In the present study we report that the expression of Fos can be induced by cocaine challenge in intrastriatal grafts derived from cell suspensions of embryonic striatal primordia. Fos-like immunoreactivity in the nuclei of grafted neurons was detected 2 hr after the injection of 50 mg/kg cocaine into the host rats. Neurons with Fos-immunoreactive nuclei tended to form clusters in the striatal grafts. The Fos-rich clusters were aligned with acetylcholinesterase (AChE)-rich and tyrosine hydroxylase (TH)-rich patches demonstrated in adjoining sections. Previous studies have shown that presynaptic and postsynaptic cellular markers of the dopaminergic system in the striatum, including immunostaining for TH and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein (DARPP-32), and binding for high affinity dopamine uptake sites and for dopamine D1 and D2 receptor sites, are all concentrated in the AChE-rich patch regions (P regions) of such embryonic striatal grafts. The preferential expression of Fos in neurons of the P regions of the grafts thus implies that the induction of Fos was cell-type specific in being concentrated in the parts of the grafts that express striatal phenotype and that are innervated by catecholamine-containing fibers.(ABSTRACT TRUNCATED AT 250 WORDS)