Twenty-nine patients with tardive dyskinesia (n = 20) or related syndromes [spontaneous dyskinesia (n = 3), levodopa-induced dyskinesia (n = 3), tardive dystonia (n = 3)] were treated with clonidine. Clinical effects of this drug were observed for up to 4 years. Seventy-five percent of patients showed at least moderate improvement, and in 50% of patients, full resolution occurred. In most cases, patients received concomitant medications, including neuroleptics and benzodiazepines. Two patients received clonidine alone, and dyskinesia was only minimally improved; however, when bromocriptine was added, prompt improvement occurred on this combined regimen. On the basis of these findings, we suggest that not only receptor supersensitivity of dopaminergic neurons but also involvement of noradrenergic neurons is important in the pathophysiology of tardive dyskinesia and related syndromes.