The use of an intramedullary alignment rod in the distal part of the femur is an important step in performing total knee-replacement arthroplasty. On the basis of our observation of a sudden decrease in oxygen saturation in some patients after insertion of the rod, a prospective study was done of the circulatory and blood-gas changes that were associated with insertion in thirty-five patients. We examined the effects of the use of an eight-millimeter solid alignment rod, with and without venting; an eight-millimeter fluted alignment rod, with venting; and an eight-millimeter fluted or solid alignment rod, inserted through a 12.7-millimeter drill-hole, but without other venting. A statistically significant reduction in oxygen saturation, arterial oxygen tension (PaO2), and end-tidal carbon-dioxide tension (PETCO2) occurred after insertion of both solid and fluted eight-millimeter alignment rods through an eight-millimeter hole in both vented and unvented femoral canals, in association with a significant increase (p < 0.01) in intramedullary pressure. Bone-marrow contents and fat were retrieved from samples of blood from the right atrium, indicating that embolization of marrow contents had occurred during insertion of the alignment rod. A small decrease in systemic blood pressure and heart rate also occurred. These changes were completely eliminated by the use of a 12.7-millimeter drill-hole as the entry site of the eight-millimeter fluted rod. We concluded that insertion of an intramedullary alignment rod in the femur causes embolization of marrow contents, which decreases arterial oxygen tension, oxygen saturation, end-tidal carbon-dioxide tension, arterial blood pressure, and heart rate. This embolization can be prevented by making the drill-hole that is used as the entry site of a fluted alignment rod at least 4.7 millimeters larger than the diameter of the rod.