Numbers and areas of neuronal profiles from sections of brain stem at specific anatomic levels of the locus coeruleus and the dorsal raphe nucleus were measured in 33 patients with Huntington's disease and in 23 age-matched control subjects. Results from the Huntington's disease cases were correlated with severity of neostriatal atrophy and with systematically collected quantitative clinical data. Among the patients with Huntington's disease, lower locus coeruleus neuronal counts, reduced neuronal areas, and reduced locus coeruleus length (distance between rostral and caudal levels) were associated with features of advanced disease, including severity of neostriatal atrophy, severity of dementia, duration of illness, and severity of motor impairment and activities of daily living impairment. By contrast, there was no evidence of neuronal pathology within the dorsal raphe nucleus in Huntington's disease. Pathologic changes in the locus coeruleus may relate to some of the clinical manifestations of Huntington's disease.