There is mounting evidence that tumour necrosis factor (TNF) is involved in the early phase of inflammatory response, but its relation to histamine action is unclear. In this study we examined the effect of drugs interfering with TNF expression (thalidomide) and activity (infliximab) and compared it to that of a H(1)R histamine receptor antagonist (loratadine) in a model of histamine-induced rat hind-paw oedema formation. Systemic administration of all three drugs effectively reduced the oedema formed by the subsequent transplantar administration of histamine into the rat paw, in a dose-dependent manner. The time-dependence of the effect exerted by thalidomide and infliximab was very similar to that of loratadine. Moreover, there appears no significant synergistic effect between infliximab and loratadine, suggesting that TNF is either a major modulator or a direct mediator of oedema formation induced by histamine, in the rat paw.