The present study was performed to determine the effect of a nearly complete nigrostriatal dopaminergic denervation on DARPP-32 levels in the striatum from animals and parkinsonian patients. DARPP-32 levels were estimated by in vitro phosphorylation in the presence of cAMP, or after inactivation of endogenous kinases and phosphatases, in the presence of the catalytic subunit of cAMP-dependent protein kinase. Intranigral 6-hydroxydopamine (6-OHDA) infusion in rats, or peripheral administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets, did not change striatal DARPP-32 levels. Postmortem studies, carried out on brains obtained shortly after death, from patients with Parkinson disease, or from patients with progressive supranuclear palsy, showed that the levels of striatal DARPP-32 were not different from controls. These results indicate that dopaminergic striatal denervation did not modify the amount of DARPP-32 in the striatum, suggesting that the expression of DARPP-32, a protein which mediates some of the effects of dopamine in striatal neurons, is independent from the dopaminergic innervation.