Cortical projections provide the major excitatory inputs to the striatum. In addition to innervating medium spiny cells, these axons contact striatal interneurons that are parvalbumin-immunoreactive (PV-ir). PV-ir interneurons make synaptic connections with many medium spiny cells, and thus can modulate striatal output. The striatum also receives dopaminergic projections from the substantia nigra, but it has been challenging to study the impact of dopamine (DA) cell injury on corticostriatal activity in vivo due to limitations in the methods used to induce cortical activity. Using epidural application of the GABA(A) antagonist picrotoxin, which produces a topographically restricted region of striatal immediate-early gene expression, we have investigated the effect of DA cell injury or DA receptor antagonism on immediate-early gene (IEG) expression in striatal medium spiny cells and PV-ir interneurons. Epidural application of picrotoxin to the rat's M1 motor cortex induced Fos in ipsilateral dorsolateral striatum. Animals previously given 6-hydroxydopamine (6-OHDA) injections into the ascending DA pathways had greater total numbers of cortical stimulation-induced striatal Fos-ir cells but fewer Fos-ir/PV-ir cells, compared to sham-operates. In a separate experiment, rats given cortical stimulation and treated with the DA D2-class antagonist eticlopride (0.10 mg/kg) exhibited fewer Fos-ir/PV-ir cells than did vehicle-treated rats. Taken together, these results indicate that DA may importantly control striatal output via influences on PV-ir interneurons. Possible mechanisms for these influences are discussed.