Simultaneously obtained blood samples from the coronary sinus and systemic arterial circulation were analyzed for antithrombin III (ATIII) activity and fibrinopeptide A (FpA) concentration in nine patients undergoing elective PTCA in order to determine the effects of locally delivered heparin. Samples were obtained at the following designated times: prior to the administration of systemic heparin (period I); 5 min following a loading dose of systemic heparin (period II); 5 min following the final balloon inflation but prior to local delivery (period III); and 5 min following the administration of 4,000 units of unfractionated heparin using a local delivery catheter system (period IV). We found consistent increases in both systemic arterial (P = 0.006) and coronary sinus (P = 0.0002) ATIII activity with systemic heparinization designed to prolong the activated clotting time to 300 sec. However, local delivery of heparin further increased coronary sinus ATIII activity (P = 0.003, period III vs. period IV). FpA concentration decreased in both systemic arterial (P < 0.0001) and coronary sinus (P < 0. 0001) samples following systemic heparinization. Moreover, local delivery of heparin further decreased coronary sinus FpA concentration (P = 0.04). Thus, on a background of intense anticoagulation during PTCA, the local delivery of 4,000 units of unfractionated heparin confers incremental antithrombotic activity. Cathet. Cardiovasc. Intervent. 48:84-88, 1999.