Substance P (SP) levels were determined by radioimmunoassay (RIA) in several regions of post-mortem brain of controls and Huntington's disease (HD) patients. In controls, highest SP levels were found in basal ganglia, substantia nigra and hypothalamus. Nigral pars reticulata contained 3--4-fold higher levels than pars compacta. In HD, SP levels were reduced in all basal ganglia and substantia nigra. The reductions ranged from 48% in caudate nucleus to over 90% in nigral pars reticulata. There were no changes in SP levels in HD frontal cortex, thalamus or hypothalamus.