We hypothesized that myocardial microvascular filtration rate (Jv) could be manipulated by varying end-diastolic myocardial interstitial hydrostatic (P(int)) pressure. Dogs under general anesthesia were instrumented with intramyocardial capsules to measure P(int) and with prenodal myocardial lymphatic trunk cannulas and superior vena caval balloon-tipped catheters to manipulate myocardial lymph flow. Because, for a given surface area, the lymph-to-plasma protein concentration ration (CL/CP) varies inversely with JV, CL/CP was utilized as an index of changes in JV. When lymphatic outflow pressure (P0) was elevated to abolish lymph flow and force myocardial interstitial fluid volume to expand, P(int) rose significantly from 15.0 +/- 0.8 to 27.6 +/- 1.0 mmHg and CL/CP increased significantly from 0.75 +/- 0.04 to 0.85 +/- 0.04, indicating a decrease in JV. When P0 was lowered and lymph flow resumed, P(int) and CL/CP decreased significantly to 15.3 +/- 0.9 mmHg and 0.75 +/- 0.04, respectively, indicating an increase in JV. We conclude that myocardial microvascular filtration rate may be modulated by changes in P(int) resulting from alterations in myocardial interstitial fluid volume secondary to variations in lymph flow from the heart.