This study was undertaken to determine if coronary vascular permeability (CVP) increases and if myocardial edema develops in the canine heart after local exposure to histamine. Histamine (50 or 15 micrograms/min) or compound 48/80 (0.1-0.2 mg/kg) was infused into the left anterior descending coronary artery (LAD) of open-chest dogs, and changes in CVP were determined by comparing prenodal cardiac lymph flow (Q1) and lymph-to-plasma protein concentration ratio (C1/Cp) before and during histamine or compound 48/80 treatment. CVP increased in most, but not all, experiments with both doses of histamine as indicated by simultaneous increases in both Q1 and C1/Cp. The injection of compound 48/80 into the LAD of four dogs caused unequivocal increases in CVP in only one experiment. Compared with the effect of histamine on the forelimb, the average increases in Q1 and C1/Cp were not large with either histamine or compound 48/80, which suggests that the increases in CVP were relatively small. Moreover, edema did not develop. These results indicate that the coronary microvasculature of the intact dog heart is relatively insensitive to increases in permeability produced by histamine. Furthermore, the release of histamine from myocardial mast cells would not be expected to play a major role in the myocardial edema that develops under various pathological conditions.