Interstitial fluid pressure (P_if) has been studied in rat nasal mucosa during early inflammatory reactions induced by dextran anaphylaxis and local application of histamine. P_if was measured by using sharpened micropipettes connected to a servo-controlled counterpressure system. Access to the nasal mucosa was obtained from the facial side of the head through a small cavity drilled in the nasal bone. During dextran anaphylaxis, P_if increased significantly from control values of 2.2 ± 0.4 to 3.8 ± 0.21 mmHg (P < 0.05) within 1 h. Corresponding P_if values for histamine were 1.6 ± 0.9 and 2.9 ± 0.9 mmHg (P < 0.05), respectively. These measurements support the hypothesis that a major driving force for the rapid exudation across inflamed respiratory mucosa is a hydrostatic pressure gradient created by increased mucosa P_if. When the transvascular fluid shifts accompanying the inflammatory reactions are prevented by circulatory arrest, P_if decreased significantly to subatmospheric values, 0.8 ± 0.8 and 3.3 ± 1.2 mmHg in the dextran and histamine group, respectively (P < 0.05). The decrease in P_if in the nasal mucosa after inflammatory stimuli, during circulatory arrest, provides further evidence for "active" modulation of P_if through changes in mechanical properties of the interstitial matrix. The decrease in P_if seen under these circumstances reveals a possible mechanism participating in the rapid and initial edema formation after inflammatory provocations.