This study investigates the effects of histamine and serotonin on vascular permeability in rats using electron microscopy. Histamine and serotonin were injected subcutaneously into the scrotum, where they diffused into the underlying cremaster muscle. An intravenous injection of colloidal HgS was used to track leaks. After various intervals, the animals were sacrificed, and the cremaster was examined under an electron microscope. Histamine and serotonin caused endothelial gaps in blood vessels, with gaps ranging from 0.1 to 0.8 micra wide. These gaps allowed fluid to pass through but retained larger particles, suggesting the basement membrane acted as a filter. Tracer particles accumulated against the basement membrane, indicating fluid leakage. Phagocytosis by endothelial cells was minimal, but pericytes were actively phagocytic. At 3 hours, no leaks were found. Histamine and serotonin caused similar effects, though serotonin was more potent. The study found that endothelial cells became partially disconnected along intercellular junctions, supporting the idea of intercellular leaks. Light microscopy confirmed these findings, showing tracer particles and intercellular junctions. The lipid nature of chylomicra was confirmed using light microscopy. The study highlights the role of histamine and serotonin in increasing vascular permeability, a key aspect of acute inflammation. The findings suggest that endothelial cells become partially disconnected along intercellular junctions, leading to leaks. The basement membrane acts as a filter, allowing fluid to pass but retaining larger particles. The study also notes that the smallest vessels (3-5 micra) did not develop leaks, while larger vessels (7-10 micra) were more susceptible. The results indicate that the mechanism of vascular permeability involves intercellular junctions and the basement membrane's filtering function. The study provides evidence that histamine and serotonin cause endothelial gaps, leading to fluid leakage and the accumulation of tracer particles. The findings contribute to understanding the pathogenesis of vascular leaks in inflammation.This study investigates the effects of histamine and serotonin on vascular permeability in rats using electron microscopy. Histamine and serotonin were injected subcutaneously into the scrotum, where they diffused into the underlying cremaster muscle. An intravenous injection of colloidal HgS was used to track leaks. After various intervals, the animals were sacrificed, and the cremaster was examined under an electron microscope. Histamine and serotonin caused endothelial gaps in blood vessels, with gaps ranging from 0.1 to 0.8 micra wide. These gaps allowed fluid to pass through but retained larger particles, suggesting the basement membrane acted as a filter. Tracer particles accumulated against the basement membrane, indicating fluid leakage. Phagocytosis by endothelial cells was minimal, but pericytes were actively phagocytic. At 3 hours, no leaks were found. Histamine and serotonin caused similar effects, though serotonin was more potent. The study found that endothelial cells became partially disconnected along intercellular junctions, supporting the idea of intercellular leaks. Light microscopy confirmed these findings, showing tracer particles and intercellular junctions. The lipid nature of chylomicra was confirmed using light microscopy. The study highlights the role of histamine and serotonin in increasing vascular permeability, a key aspect of acute inflammation. The findings suggest that endothelial cells become partially disconnected along intercellular junctions, leading to leaks. The basement membrane acts as a filter, allowing fluid to pass but retaining larger particles. The study also notes that the smallest vessels (3-5 micra) did not develop leaks, while larger vessels (7-10 micra) were more susceptible. The results indicate that the mechanism of vascular permeability involves intercellular junctions and the basement membrane's filtering function. The study provides evidence that histamine and serotonin cause endothelial gaps, leading to fluid leakage and the accumulation of tracer particles. The findings contribute to understanding the pathogenesis of vascular leaks in inflammation.