Previously, we reported the production and characterization of fos-lacZ transgenic mice [41] and rats [19] that can be used to monitor both constitutive and evoked expression of c-fos in vivo. When we compared the sites of spontaneous fos-lacZ expression in the brains of developing transgenic fos-lacZ mice and rats, the patterns were almost identical. However, throughout the first postnatal month, the rat striatum contained a large number of Fos-lacZ-positive cells whereas only a few positive cells were seen in the mouse. By adulthood, the number of Fos-lacZ-positive cells in the rat striatum had declined dramatically to the low basal values seen in mice. To establish whether this species difference was evident in the adult striatum, rats and mice were treated with metamphetamine. This indirect D1 agonist, triggered a pronounced induction of fos-lacZ in the rat striatum while only a modest response was observed in the mouse. These data imply: (1) there are differences in dopamine-dependent stimulus-transcription coupling between the two species. (2) Maturation of dopaminergic signalling pathways may underlie the spontaneous immediate-early gene response in the developing rat striatum.