We investigated whether various recombinant cytokines induce vascular hyperpermeability when intradermally injected into rats. Only TNF did so. Of the other cytokines examined (IL-1, IL-2, granulocyte-CSF, IFN-alpha, IFN-beta, IFN-gamma) none had this effect. The increase in vascular permeability was dose dependent, and the peak response was observed at 90 min after TNF injection. When mixtures of TNF and various other cytokines (IL-1, IL-2, granulocyte-CSF, IFN-alpha, IFN-beta, IFN-gamma) were injected, only IL-1 and IFN-gamma augmented TNF-induced vascular hyperpermeability, the increase occurring in a dose-dependent manner. The induction of vascular hyperpermeability by TNF and its enhancement by IL-1 and IFN-gamma were inhibited by selective depletion of peripheral blood neutrophils with i.p. administration of an anti-rat neutrophil mAb, RP-3. Reconstitution of neutrophils to the depleted rats by in situ injection of these cells, restored TNF increased vascular permeability.