These studies indicate that tumor necrosis factor-α (TNFα) alters albumin permeability and unlike bradykinin (BK) the increased albumin permeability lasts for the duration of the application. Neither agonist requires the presence of white blood cells or other blood-borne substances to produce this inflammatory response. These experiments were completed in the in situ, microcannulated, perfused venules of the mesentery in the anesthetized hamster. Albumin transport was measured using intravital fluorescence microscopy, TRITC-labeled albumin, and densitometric tracking. Further, by varying the intravascular pressure, the hydraulic (L(p)(1 - σ)) and diffusive permeability (P0) coefficients of these microvessels were determined. Both BK and TNFα produced an increase in albumin flux, which was dependent upon the dose and time domains. This response was present when the agonists were given by either intra- or extravascular presentation. Both hydraulic coupling and microvascular permeability were increased by BK and TNFα. TNFα increased albumin permeability rapidly and its effect lasted as long as TNFα was present, whereas the increased albumin transport by BK was biphasic. The results implicate a dynamic modification in the microvascular wall to these inflammatory agonists and the mechanism(s) for transduction in the endothelium are quite different.