Levels of preproenkephalin (PPE) mRNA were measured in different sectors of the striatum with in situ hybridization histochemistry in both normal and parkinsonian (MPTP-treated) squirrel monkeys. In parkinsonian monkeys, a marked increase in PPE mRNA levels was noted in the dorsolateral third of the precommissural putamen and in most of the postcommissural putamen. These regions largely correspond to the sensorimotor striatal territory. The other striatal sectors, including the caudate nucleus, did not exhibit significant changes, despite the fact that the loss of the dopaminergic input was severe in most of the striatum. These results reveal that PPE mRNA expression is specifically altered in striatal regions involved in sensorimotor processing in parkinsonian monkeys.