Interleukin (IL)-l inhibits the function of insulin-producing rat pancreatic beta-cellsin vitroandin vivo, and it has been postulated that the IL-1 effect is mediated through the cytokine inducable nitric oxide (NO) synthase. IL-1 inhibits the function of cultured human thyroid cells too, and in this study human thyroid cell production of NO in response to the TSH-stimulated influence of IL-1β(105U/1) and TNF-α(106U/1), alone or in combination was measured. IL-1β, but not TNF-α, induced an increase in nitrite production, which was significantly reduced by the competitive inhibitor of nitric oxide synthase L-NG-monomethyl-arginine (L-NMMA) (0.1 mmol/L and 0.5 mmol/L). However, the nitrite production was unrelated to the IL-1β-induced inhibition of thyroglobulin (Tg) and cyclic AMP (cAMP) and the IL-1β-induced IL-6 production. Thus, it is unlikely that NO is a second mediator of the demonstrated effects of IL-1βand TNF-αon human thyroid cells in culture.