The effect of heparin (5 U/ml) on platelet function was examined by hemostatometry in vitro. A wide individual variation of this effect was found in 290 patients who underwent cardiac operations: 8.6% (25) experienced a proaggregatory effect, 58.6% (170) experienced a mild to moderate inhibition of platelet function, and 32.8% (95) experienced a severe inhibition. No significant difference was found among patient characteristics, including antiplatelet medication, in these three subgroups. In vitro measurements correlated significantly with ex vivo measurements, that is, from blood taken after heparinization (p < 0.0001; r = 0.97, n = 15). In III patients who underwent cardiac surgical intervention, a significant correlation (p < 0.0001; 0.4 < r < 0.52) was found between preoperative measurements of the degree of inhibition of platelet function by heparin and the total postoperative blood loss after 4, 12, and 18 hours. Similarly, there was a significant difference (p < 0.0001) in the total blood loss at 4, 12, and 18 hours between the subgroups that showed, in vitro, a mild to moderate inhibition of platelet function preoperatively compared with a severe inhibition (713 +/- 43 ml versus 1172 +/- 76 ml at 18 hours). It is concluded that platelet inhibition as a result of heparin varies among patients and appears to be a previously unrecognized etiologic factor in bleeding after cardiopulmonary bypass.