In isolated working rat hearts we have evaluated the effects of preconditioning on postischemic coronary endothelial permeability. Isolated Wistar male rat hearts were used and subdivided into three groups: Group A, control hearts submitted to 20 min global normothermic ischemia; Group B, hearts subjected, before ischemia, to preconditioning (three phases of 3 min ischemia, each one followed to 2 min Langendorff reperfusion; Group C, hearts submitted to preconditioning and hypertonic reperfusion (by adding 80 mM sucrose to normal perfusion buffer), in order to increase the effects on postischemic interstitial fluid accumulation (osmotic forces balance). A 65 min working heart reperfusion was also performed to assess functional response. We have evaluate the hemodynamic changes (coronary and aortic flows, systolic aortic pressure, work minute), reperfusion arrhythmias, heart weight changes (ww/dw), myocardial enzyme release (creatine phosphokinase and lactic dehydrogenase) and microcirculation permeability changes (FITC.albumin diffusion), as an index of endothelial function. In Group B, a significant reduction of ischemia-reperfusion damage (functional recovery, enzyme release and arrhythmias) was detected with respect to Group A. In Group C this reduction was significantly more evident with respect to groups A and B. In Groups B and C, a significant reduction in myocardial reperfusion (ww/dw: A: 5.9 +/- 0.5, B: 4.9 +/- 1.1, p < 0.02 vs A, C: 4.4 +/- 0.6, p < 0.01 vs A) edema and FITC-albumin diffusion (A: 32.8 +/- 5.9% area; B: 16.3 +/- 6.1% area, p < 0.01 vs A; C: 13.3 +/- 4.5% area, p < 0.01 vs A), especially in perimyocytic space was also observed. Data show that preconditioning may exert a cardioprotective effect by reducing endothelial postischemic functional alterations (vascular permeability) and reperfusion edema. The importance of fluid diffusion within the interstitium in the development of reperfusion damage is supported by better postischemic recovery in Group C, in which an interference on osmotic load was performed.