We measured plasma dopamine-beta-hydroxylase (DBH) activity; norepinephrine, dopamine and their metabolites in cerebrospinal fluid (CSF); and indices of brain atrophy on CT scans in patients with and without tardive dyskinesia (TD). Patients with TD had greater plasma DBH activity and higher CSF-norepinephrine than non-TD patients. The two groups were similar in CSF-dopamine and its metabolites. Among patients with low plasma-DBH activity, those with TD had greater ventricular enlargement and higher bifrontal-bicaudate ratio, suggesting greater subcortical atrophy as compared with non-TD patients. These findings suggest that TD may be a heterogeneous syndrome, with subgroups characterized by noradrenergic hyperactivity or subcortical atrophy.