Four patients out of twenty with renal cancer and melanoma undergoing cancer immunotherapy with interleukin 2 (IL-2) and interferon alpha-2 (IFN-alpha-2) had laboratory evidence of hypothyroidism starting at cycle three to six, with a decline in serum thyroxine below normal and, in three cases, a rise in serum thyrotropin and thyroglobulin. One hypothyroid patient had elevated serum antimicrosomal antibody titres before the start of treatment and two others responded similarly during therapy. Three of the sixteen euthyroid patients also developed elevated titres of this antibody. Partial or complete remission was observed in seven of the patients-three of the four with hypothyroidism showed tumour regression. Thus IL-2 and IFN-alpha-2 can cause hypothyroidism, presumably via induction or exacerbation of autoimmune thyroid reactions. The occurrence of hypothyroidism may be mediated by high-dose IL-2 (rather than by LAK cell therapy as previously suggested) and potentiated by IFN-alpha-2.