A method that combines high performance liquid chromatography with radioimmunoassay (HPLC/RIA) has been used to characterize neurotensin-like immunoreactivity (NT-IR) in the basal ganglia from control subjects and Parkinson's disease (PD) patients. In samples from the caudate nucleus and putamen, NT-IR eluted as two HPLC peaks. One was indistinguishable from the synthetic tridecapeptide, while the other peak corresponded to oxidized NT, as judged by its chromatographic behaviour and its reaction with the antiserum employed. There were marked discrepancies between the IR detected in crude extracts and that in HPLC purified samples. NT levels (HPLC/RIA) were unaltered in the caudate nucleus, putamen and both segments of the globus pallidus in the parkinsonian brain. In contrast, there was a two-fold increase in NT content in both zona compacta and zona reticulata of the substantia nigra in PD patients compared to controls. Degeneration of the nigrostriatal pathway and/or prolonged antiparkinsonian treatment in PD appears to alter neurotensin levels in an attempt to activate the dopaminergic nigrostriatal pathway.