Adrenaline has been shown to inhibit the release of tumor necrosis factor (TNF) elicited by lipopolysaccharide (LPS) when tested in vitro on cultured human blood cells and rat macrophages. In this report we have examined the effect of the in vivo administration of adrenaline on TNF serum levels induced by LPS. In agreement with in vitro data, adrenaline (0.1 mg/kg, s.c.) was found to inhibit in the mouse the LPS-induced TNF release. The beta-adrenergic antagonist propranolol administered 1 h before adrenaline completely blocked the adrenaline activity, whereas the alpha-adrenergic antagonist phentolamine was ineffective. These data demonstrate that: (i) adrenaline is an effective antagonist of LPS-induced TNF release in vivo, and (ii) its effect is mediated by beta-adrenergic receptors.