This retrospective study, based on 18 case reports, describes an organic affective syndrome, manic type, occurring shortly after the initiation of thyroid replacement in hypothyroid patients. The symptomatology and homogeneity of the syndrome offers insight into the relationship between thyroid activity and affective disturbance. The patients experiencing mania showed concurrent psychopathology at the time of replacement therapy, frequently had a past history of personal or familial psychiatric disorder and were given dosages in the high range of normal. The potential morbidity of the manic state was considerable. These findings suggest that a group of hypothyroid patients at risk can be identified. In such a group, lower initial dosages and gradual increases in dosage may be indicated.