The study investigates the ultrastructural basis of capillary permeability using horseradish peroxidase as a tracer in mice. The research focuses on the endothelial cell junctions and intercellular clefts in cardiac and skeletal muscle capillaries. Key findings include: 1. **Permeability Pathways**: Peroxidase was observed to permeate endothelial intercellular clefts and cell junctions, suggesting that these structures are involved in the transendothelial passage of substances. 2. **Cell Junctions**: The endothelial cell junctions were characterized as maculae occludentes, with gaps of about 40 Å in width between the maculae, rather than zonulae occludentes. This indicates that the intercellular clefts are permeable. 3. **Vesicular Transport**: Some observations support the presence of vesicular transport of peroxidase, although the evidence is not entirely convincing. Vesicles were found to be stained in various stages after peroxidase injection, suggesting their role in substance transport. 4. **Control Experiments**: Controls were conducted to exclude artificial adsorption of peroxidase and to assess vascular leakage induced by histamine and serotonin. No significant leakage was observed, indicating that peroxidase did not cause abnormal vascular permeability. 5. **Ultrastructure of Cell Junctions**: The ultrastructure of endothelial cell junctions was examined, showing that the width of the intercellular cleft was typically 100-200 Å, with gaps of about 40 Å between adjacent plasma membranes. These gaps contained electron-opaque material, suggesting the presence of tight junctions. 6. **Discussion**: The study concludes that horseradish peroxidase passes across capillaries via intercellular clefts and possibly through micropinocytotic vesicles. The findings support the idea that the endothelial cell junctions are the morphological equivalent of the small pore system proposed by physiologists for the passage of small, lipid-insoluble molecules across the endothelium. Overall, the research provides insights into the ultrastructural mechanisms underlying capillary permeability, highlighting the role of intercellular clefts and cell junctions in substance transport.The study investigates the ultrastructural basis of capillary permeability using horseradish peroxidase as a tracer in mice. The research focuses on the endothelial cell junctions and intercellular clefts in cardiac and skeletal muscle capillaries. Key findings include: 1. **Permeability Pathways**: Peroxidase was observed to permeate endothelial intercellular clefts and cell junctions, suggesting that these structures are involved in the transendothelial passage of substances. 2. **Cell Junctions**: The endothelial cell junctions were characterized as maculae occludentes, with gaps of about 40 Å in width between the maculae, rather than zonulae occludentes. This indicates that the intercellular clefts are permeable. 3. **Vesicular Transport**: Some observations support the presence of vesicular transport of peroxidase, although the evidence is not entirely convincing. Vesicles were found to be stained in various stages after peroxidase injection, suggesting their role in substance transport. 4. **Control Experiments**: Controls were conducted to exclude artificial adsorption of peroxidase and to assess vascular leakage induced by histamine and serotonin. No significant leakage was observed, indicating that peroxidase did not cause abnormal vascular permeability. 5. **Ultrastructure of Cell Junctions**: The ultrastructure of endothelial cell junctions was examined, showing that the width of the intercellular cleft was typically 100-200 Å, with gaps of about 40 Å between adjacent plasma membranes. These gaps contained electron-opaque material, suggesting the presence of tight junctions. 6. **Discussion**: The study concludes that horseradish peroxidase passes across capillaries via intercellular clefts and possibly through micropinocytotic vesicles. The findings support the idea that the endothelial cell junctions are the morphological equivalent of the small pore system proposed by physiologists for the passage of small, lipid-insoluble molecules across the endothelium. Overall, the research provides insights into the ultrastructural mechanisms underlying capillary permeability, highlighting the role of intercellular clefts and cell junctions in substance transport.