In this study, we have examined the effects of chronic L-3,4-dihydroxyphenylalanine (L-DOPA) administration on the remaining dopaminergic neurons in rats with 6-hydroxydopamine (6-OHDA) or buffered FeCl3 partial lesions to the nigrostriatal tract. L-DOPA administration increased the turnover of dopamine in the striatum. L-DOPA administration for 1 week produced an increase in the level of striatal RTI-121 binding, a specific marker for dopamine uptake sites on the dopaminergic nerve terminals in the striatum. However, longer periods of L-DOPA treatment decreased the level of RTI-121 binding in the striatum. In the partial 6-OHDA lesion model, L-DOPA treatment had a time-dependent effect on the number of neurons demonstrating a dopaminergic phenotype i.e., neurons that are tyrosine hyrdoxylase (TH)-immunopositive, on the lesioned side of the brain. In the first few weeks of treatment, L-DOPA decreased the number of TH-positive neurons but with long-term treatment, i.e., 24 weeks, L-DOPA increased the number of neurons demonstrating a dopaminergic phenotype. Even in the buffered FeCl3 infusion model, where the levels of iron were increased, L-DOPA treatment did not have any detrimental effects on the number of TH-positive neurons on the lesioned side of the brain. Consequently, chronic L-DOPA treatment does not have any detrimental effects to the remaining dopaminergic neurons in rats with partial lesions to the nigrostriatal tract; indeed in the 6-OHDA lesion model, long-term L-DOPA may increase the number of neurons, demonstrating a dopaminergic phenotype. © 2001 Movement Disorder Society.