Protamine has been used for neutralizing heparin and its dosage is decided by the initial fixed dose of heparin. Adequate protamine neutralization is very important to reduce complications. To attenuate excess reactions, in particular, whole blood heparin concentration during and after cardiopulmonary bypass was measured using Hepcon, and the efficacy of optimal protamine dose in open heart surgery was evaluated. Twenty patients were randomly divided into two comparable groups, P and C. In the C group, heparin was neutralized with an initial fixed dose of protamine, 1.67 mg protamine per milligram total heparin (n = 8). In the P group, protamine dose was determined for residual heparin concentration (n = 12). In the P group, blood heparin concentrations at 60 minutes after the establishment of cardiopulmonary bypass, just after cardiopulmonary bypass and first protamine administration were 2.35 +/- 0.14, 2.31 +/- 0.17 and 0.13 +/- 0.08 U/ml, respectively. Concentrations reached zero with the second protamine administration. The requirement of transfusion (659 +/- 224 vs. 1559 +/- 323 ml, p = 0.0314), pulmonary vascular resistance index just after the protamine administration (190 +/- 22 vs. 286 +/- 18 dyne.s.cm-5.m2, p = 0.0137) and the IL-8 levels (just after protamine: 26.9 +/- 5.1 vs. 43.5 +/- 5.9 pg/ml, p = 0.0499, 12 hours after cardiopulmonary bypass: 37.1 +/- 12.1 vs. 86.8 +/- 20.0, p = 0.0435) in the P group were significantly lower than those in the C group. These data suggested that heparin level monitoring in whole blood may be useful to determine the optimal dose of protamine resulting in the decrease of a requirement of blood components in open heart surgery and attenuating in transient pulmonary hypertension and excess protamine-induced inflammatory reactions.