Tests of thyroid function and pathology were carried out on 133 patients before they were treated with lithium (Li+). Of the 12 patients who subsequently became hypothyroid during treatment with lithium 9 had, before the commencement of treatment, thyroid autoantibodies and/or an exaggerated thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH), whereas 3 patients had neither of these indicators. Lithium administration was accompanied by a rise in thyroid antibody titre in 20 patients but a fall in only 5, a statistically significant difference. Evidence that it may be an immunostimulant is discussed. Li+-induced thyroid failure cannot be accurately predicted, and may occur suddenly. The best minimum safeguard, therefore, is serial thyroxine (T4) (or free T4) estimation, supplemented if equivocal by a free thyroxine index (FTI), a basal TSH and, if doubt remains, by a TRH test.