We examined the prevalence of antimicrosomal and antithyroglobulin antibodies in psychiatric inpatients with unipolar depression (N = 218), bipolar disorder manic (N = 51), bipolar disorder depressed (N = 19), and bipolar disorder mixed (N = 26) in comparison with two control groups: psychiatric inpatients with adjustment disorder (N = 80) and family medicine outpatients without current psychiatric illness (N = 144). A statistical analysis that controlled for age and sex revealed the frequency of positive antibody titers not to be increased in patients with a diagnosis of unipolar depression (6.9%) or bipolar disorder manic (3.9%), when compared with patients with adjustment disorder (2.5%) and non-psychiatric subjects (6.9%). There was a weak trend toward an increased prevalence of antithyroid antibodies in patients with bipolar disorder, mixed (19%) or depressed subtype (16%). The excess occurrence of antibodies in patients with either mixed or depressed bipolar disorder did not appear to be related to lithium exposure, which was similar in all bipolar subgroups. When the intervening influences of age and sex are taken into account, unipolar depression does not appear to be associated with an excessive rate of antithyroid antibodies; however thyroid autoimmunity may be weakly associated with subtypes of bipolar disorder in which depressive symptoms are prominent.