Interleukin (IL)-1, tumour necrosis factor (TNF)-α and interferon (IFN)-γ 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-α, TNF-β and IFN-γ all inhibited thyroglobulin (Tg) and cAMP production from cultured human thyroid cells. When TNF-α was added simultaneously with IL-1β, the highest concentration of TNF-α (10⁶ U/l) enhanced the inhibition of Tg and cAMP induced by IL-1β (1-10⁵ U/l). TNF-β had no influence on IL-1β-induced inhibition. IFN-γ (10⁴ U/l) added together with IL-1β in lower concentrations (1-10² U/l) stimulated cAMP production, while at high concentrations of IL-1β (10⁵ U/l), IFN-γ enhanced the inhibitory influence of IL-1β on Tg production. The hormones of the immune system, IL-1, TNF and IFN-γ, may thus contribute to the decreased thyroid function characteristic of some thyroid inflammatory diseases.