Sixteen days after a unilateral lesion of the ventromedial tegmentum (VMT) of the midbrain, adult cats received an intravenous dose of L-DOPA (20 mg/kg), and the caudate nucleus from each hemisphere was removed at various time intervals thereafter. In the caudate nucleus contralateral, to the VMT lesions, DA levels reached 200% of control values within 15 min, and maintained this elevation for at least 2 hours. DA levels in the caudate nucleus ipsilateral to the VMT lesion were much lower than contralateral values; however, they were much higher than those of non-DOPA treated animals with comparable lesions. DA levels in the caudate nucleus of the lesioned hemisphere were directly related to the remaining DOPA decarboxylase activity. The striatal serotonin concentrations were unchanged after L-DOPA, but an increase in 5-hydroxyindoleacetic acid levels was observed. From these results, we conclude that, (i) in cats with nigrostriatal tract lesions after low doses of L-DOPA comparable to those given to patients with Parkinson's disease, the bulk of the newly formed DA in the caudate nucleus is contained in nigrostriatal neurons, and (ii) there exists an inverse relationship between the ability of the caudate to synthesize DA and the severity of the nigrostriatal tract lesion.