Interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been demonstrated in thyroid tissue. We have previously shown that high concentrations of IL-1 inhibit and low concentrations stimulate human thyroid cell function in vitro. In the present study, TNF-alpha, TNF-beta and IFN-gamma all inhibited thyroglobulin (Tg) and cAMP production from cultured human thyroid cells. When TNF-alpha was added simultaneously with IL-1 beta, the highest concentration of TNF-alpha (10(6) U/l) enhanced the inhibition of Tg and cAMP induced by IL-1 beta (1-10(5) U/l). TNF-beta had no influence on IL-1 beta-induced inhibition. IFN-gamma (10(4) U/l) added together with IL-1 beta in lower concentrations (1-10(2) U/l) stimulated cAMP production, while at high concentrations of IL-1 beta (10(5) U/l), IFN-gamma enhanced the inhibitory influence of IL-1 beta on Tg production. The hormones of the immune system, IL-1, TNF and IFN-gamma, may thus contribute to the decreased thyroid function characteristic of some thyroid inflammatory diseases.