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During intramedullary manipulation, 2 main phenomena occur. A dramatic rise in intramedullary pressure occurs followed by intravasation of damaged marrow tissue. There are concerns about the development of increased interosseous pressure during reaming and the potential for this to contribute to fat embolism syndrome. The intramedullary pressures generated with various intramedullary devices was determined and the effects of a fracture, with and without proximal and distal venting on these pressures were studied. Pressures generated in 78 embalmed anatomic specimen femurs and tibias were studied, leaving all soft tissues intact. Pressures were recorded for awl, guide rod, reamer, and nail insertion. Venting was done by creating a 4.5-mm hole in the cortex directly opposite the transducer. Proximal venting reduced proximal pressures to 80 mm Hg in the tibia (90% reduction) and 460 mm Hg in the femur (70% reduction). Distal venting reduced distal pressures to 65 mm and 30 mm in the tibias and femurs, respectively (90% reduction in pressures). Intramedullary pressures generated during nail or alignment rod insertion in anatomic specimen bone greatly exceeds the critical thresholds (150 mm Hg) thought to be responsible for fat emboli to the lung in the dogs. The introduction of a vent may reduce the chance of fat embolism. Despite the high association of raised intramedullary pressures and fat emboli in animal studies, there is no known critical threshold for humans. Therefore, although venting seems effective in reducing the intramedullary pressure in anatomic specimen bones, its efficacy in the patient with trauma remains to be determined.