There is evidence that reduced melatonin secretion is associated with the pathophysiology of tardive dyskinesia (TD). To investigate the relationship between melatonin secretion and TD, I evaluated scores of subtypes of TD with CT scan measurements of pineal calcification (PC) size in 77 chronic institutionalized schizophrenic and bipolar patients. There was a significantly greater incidence of pathologically enlarged calcified pineal glands (greater than 1 cm in diameter) in the patients (18.1%) compared to the reported incidence in the literature in nonpsychiatric subjects (1%). In addition, there was a significant association between scores of limb-axial (but not orofacial) dyskinesias and the presence of pathologically enlarged PC (p less than 0.05). These findings support the notion that the pathophysiology of orofacial dyskinesias may be distinct from limb-axial dyskinesias. In addition, since it is possible that a pathologically enlarged calcified pineal gland is associated with reduced melatonin secretion, these findings add further support to implicate decreased melatonin secretion in the pathophysiology of TD. Further studies using direct measurements of plasma melatonin levels are required to define more precisely the relationship between TD and melatonin secretion.