High levels of angiotensin converting enzyme (ACE) are found in the caudate-putamen (CPu), globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata; these structures were connected by a continuous band of ACE. In order to investigate whether ACE was associated with dopaminergic projections from the substantia nigra or striatal projections, we performed unilateral excitotoxin lesions using N-methyl-d-asparate (NMDA) (500 nmol) into the CPu and 6-hydroxydopamine (60HDA) (8 μg) lesions of the substantia nigra. One week after the nigral 60HDA lesions and 2 weeks after the striatal NMDA lesions, 20 μm frozen brain sections were analysed by computerized quantitative in vitro autoradiography using the radioligand [125I]351A to label ACE. ACE was unchanged by nigral 60HDA lesions although a 67% decrease in the concentration of dopamine was detected in the CPu of the lesioned side. However, striatal NMDA lesions produced a significant decrease (36-54%) of ACE in the CPu, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata on the lesioned side. In these brains, ACE was unchanged in other remote regions such as the paraventricular and supraoptic nuclei. This study demonstrates that part of brain ACE is associated with neurones and terminals which descend from the CPu and globus pallidus to the substantia nigra. Since these pathways do not appear to contain angiotensin II, it is possible that ACE is involved in processing some other neuropeptide, possibly substance P, which has been shown to be a substrate for ACE and to exist in striato-nigral projections.