By using in situ hybridisation we examined the acute effects of caffeine on haloperidol-induced c-fos mRNA in rat striatum. A homogeneous induction of striatal c-fos mRNA was found 30 min after injection of haloperidol (1 mg kg(-1)). At this timepoint caffeine (40 mg kg(-1)) did not affect c-fos mRNA in striatum but caused a significant increase of this gene in the somatosensory cortex. When caffeine was injected together with haloperidol c-fos mRNA was reduced in the medial part of the striatum, but enhanced in the caudal part. Similar region-specific effects of caffeine were observed on c-fos mRNA induced by the selective dopamine D2 antagonist raclopride (0.5 mg kg(-1)). Both haloperidol and raclopride counteracted caffeine-induced c-fos mRNA expression in somatosensory cortex. By contrast no significant interactions between caffeine and the dopamine D1 antagonist SCH 23390 (0.5 mg kg(-1)) on striatal c-fos mRNA expression were observed. The present data show that caffeine modulates c-fos mRNA induced by dopamine D2 receptor antagonism differentially in sensorimotor and limbic-related areas of striatum. It is suggested that this could depend upon a different action of caffeine on the cortical inputs to these two parts of the striatum.