To determine if four commercially available intravenous protamine preparations differed in their ability to bind to human anti-protamine antibody, the sera of seven protamine-insulin-dependent diabetics who had experienced life-threatening reactions to intravenous protamine and whose sera contained a mean of 67.4 μg/ml (range, 16–200 μg/ml) of antiprotamine IgG antibody were evaluated. Each serum was preincubated with buffer and 0.0014 to 1.4 mg/ml of the four protamine preparations before addition to an agarose-based solid-phase radioimmunoassay using125I-radiolabeled staph protein A as the detection protein. In the seven sera, the concentration of soluble protamine inhibiting 50% of protamine antibody (IC50) was determined by interpolating from points above and below 50% inhibition for each protamine preparation. No significant difference was found in the IC50among the four different protamine preparations (P> 0.25; Kruskal-Wallis). The authors concluded that there is no significant difference in the immunoreactivity of the four commercial protamine preparations with human antiprotamine IgG antibody. Thus, there appears to be no advantage in using a particular intravenous protamine preparation based on immunoreactivity with human antiprotamine antibody.