Several studies in organs other than the heart suggest that platelets play a role in maintenance of microvascular integrity. In an earlier study, we reported that coronary microvascular permeability to macromolecules was reduced when blood cells were added to a Krebs-albumin perfusate. At that time, we could not differentiate the contributions made by red cells and platelets. To examine the specific role of platelets in the cell effect, isolated rat hearts were perfused with a mixture of Krebs, albumin [2 g/100 ml bovine serum albumin (BSA)], and rat plasma that was either rich in platelets (PRP) or poor in platelets (PPP). For the nine PRP hearts studied, the perfusate contained an average of 10(4) platelets/microliter. For the nine PPP hearts, the perfusate contained 5 X 10(1) platelets/microliter. The left ventricular epicardial microcirculation was observed directly using intravital fluorescence microscopy, and coronary microvascular permeability to macromolecules was assessed by monitoring the transcoronary extravasation of fluorescent albumin (FITC-BSA). We found that the measure of transcoronary FITC-BSA extravasation, the (O/I) ratio, was 0.57 +/- 0.02 (n = 70 fields) for the PPP perfused hearts and 0.47 +/- 0.02 (n = 70) for the PRP hearts (P less than 0.05). The value for the PRP group was similar to that observed earlier with the red cell perfusate (0.45 +/- 0.02). These findings support the concept that platelets help maintain the normal semipermeable membrane characteristics of the coronary exchange vessels.