Heparin is the routine anticoagulant for cardiopulmonary bypass, but complications due to heparin are often reported. This study assessed argatroban as an alternative to heparin. Normothermic cardiopulmonary bypass with hemodilution was performed for 2 h in 15 dogs (mean weight, 9.8 kg) randomly assigned to 3 groups of 5 each. The controls were given heparin 200 IU x kg(-1) before cardiopulmonary bypass; group A had argatroban infused continuously at a rate of 20 microg x kg(-1) x min(-1); group H/A had half doses of both heparin (100 IU x kg(-1)) and argatroban (10 microg x kg(-1) x min(-1)). Blood samples were collected at 5 time points during the experiment. Activated clotting time, hemoglobin level, platelet counts, and serum concentrations of fibrinogen, antithrombin III, and thrombin-antithrombin III complex were measured. The platelet count was reduced significantly, and the production of thrombin-antithrombin III complex was inhibited in group H/A. Activated clotting time remained <300 sec at all time points in group A, but it was maintained at approximately 400 sec in group H/A. Fibrinogen and antithrombin III levels were reduced to half in all groups after initiation of cardiopulmonary bypass. The simultaneous use of heparin and argatroban infusion might be useful for cardiopulmonary bypass with hemodilution.