The submandibular gland is a cell-rich encapsulated organ with high transport of fluid through the interstitial space during salivation. We hypothesized that the gland is a low-compliant tissue, i.e., that a modest increase in fluid volume will produce a rise in interstitial fluid pressure (IFP) counteracting fluid filtration into the interstitium. To test this hypothesis, we measured IFP with micropipettes and glandular blood flow (GBF) with a laser-Doppler flowmeter during changes in perfusion. Clamping of the carotid artery or the jugular vein, or electrical stimulation of the sympathetic or parasympathetic nerve to the gland, induced changes in perfusion. Baseline IFP averaged 3.5 +/- 0.5 mm Hg. Clamping of the artery reduced IFP and GBF (-56.5 +/- 8.4% and -53.1 +/- 6.4%, respectively), whereas clamping of the vein decreased GBF (-21.6 +/- 14.3%) and increased IFP (141.2 +/- 27.4%). Sympathetic nerve stimulation reduced both parameters (-86.9 +/- 16.5% and -74.4 +/- 7.0%, respectively). In contrast, stimulation of the parasympathetic nerve elicited an increase in GBF (133.2 +/- 5.9%) and in IFP (173.3 +/- 41.4%). Thus, changes in vascular volume led to concomitant changes in IFP consistent with low tissue compliance, a phenomenon of importance for fluid volume regulation.