This study investigates the mechanism by which histamine and serotonin increase vascular permeability in rats using electron microscopy. The drugs were injected subcutaneously into the scrotum, diffusing into the underlying cremaster muscle. Intravenous injection of colloidal HgS was also administered to facilitate the identification of leaks. After various intervals, the animals were killed, and the cremaster was fixed, embedded, and examined. Key findings include: - Small blood vessels (3-5 microns) remained intact 1-12 minutes after injection. - Larger vessels (7-8 microns) showed endothelial openings with gaps 0.1-0.8 microns wide, often containing portions of intercellular junctions. - The basement membrane was morphologically intact and acted as a filter, retaining tracer particles while allowing fluid to escape. - Endothelial vesicles uptake of tracer particles was minimal, and phagocytosis by endothelial cells became prominent at 3 hours. - Histamine and serotonin induced similar effects, with serotonin being more potent. - Endothelial cell separation along intercellular junctions was observed, supporting the concept of intercellular leaks. - The basement membrane retained fine particulate material but allowed red blood cells to pass through, suggesting its filtering effect. The study provides strong evidence that endothelial openings induced by histamine and serotonin occur primarily along intercellular junctions, and the basement membrane acts as a filter.This study investigates the mechanism by which histamine and serotonin increase vascular permeability in rats using electron microscopy. The drugs were injected subcutaneously into the scrotum, diffusing into the underlying cremaster muscle. Intravenous injection of colloidal HgS was also administered to facilitate the identification of leaks. After various intervals, the animals were killed, and the cremaster was fixed, embedded, and examined. Key findings include: - Small blood vessels (3-5 microns) remained intact 1-12 minutes after injection. - Larger vessels (7-8 microns) showed endothelial openings with gaps 0.1-0.8 microns wide, often containing portions of intercellular junctions. - The basement membrane was morphologically intact and acted as a filter, retaining tracer particles while allowing fluid to escape. - Endothelial vesicles uptake of tracer particles was minimal, and phagocytosis by endothelial cells became prominent at 3 hours. - Histamine and serotonin induced similar effects, with serotonin being more potent. - Endothelial cell separation along intercellular junctions was observed, supporting the concept of intercellular leaks. - The basement membrane retained fine particulate material but allowed red blood cells to pass through, suggesting its filtering effect. The study provides strong evidence that endothelial openings induced by histamine and serotonin occur primarily along intercellular junctions, and the basement membrane acts as a filter.