Fibronectin (Fn), a normal serum protein which appears to have important roles in wound healing and in reticuloendothelial system function, is depressed by most types of trauma. Fn is released into the tissue at the site of an injury which suggests the depression is the result of Fn sequestration at the wound site. A competitive inhibition assay for Fn was used to measure the concentration of Fn in fluid draining the site of a radical mastectomy and the level in concurrently obtained plasma. Plasma levels of Fn were significantly depressed following surgery but were returning toward normal by 24 hours postsurgery. The concentration of Fn in drainage fluid collected two hours postop was slightly but significantly lower than the plasma collected simultaneously. By 8 hours after surgery, drainage fluid levels were significantly higher than that in concurrently obtained plasma, and the difference was even more pronounced at 24 hours postop. Fn in the drainage fluid retained opsonic activity but at a lower level than the opsonic activity in plasma. The higher concentration of Fn in drainage fluid than in plasma appears to be due to binding of the Fn to tissue debris in the exudate, which prevents the reentry of Fn into the vascular compartment.