Five fibrin-specific monoclonal antibodies have been generated using three different immunogens and a unique clot/plasma screening procedure. Two of the mAbs are directed to an epitope(s) on the A alpha-chain of fibrinogen while two others seem to react with a distinct B beta-chain epitope(s). A third antibody seems to displace all the mAbs from fibrin and may be directed to a repeating structural domain in the fibrin. The Kd values obtained (approximately 10(-9)M) using dried fibrin clots suggest high avidity for fibrin. All the mAbs cross-react with the fibrin-like X-oligomer structure in solution but in the presence of fibrin this reaction seems irrelevant due to the low Kd of the mAb/fibrin reaction. These mAbs have been examined for uptake by fibrin in a laboratory circulation circuit and while the uptake was dependent on mAb concentration an increase was noted for most concentrations over the first 2 h of circulation in the presence of plasma.