Protamine has long been used for the neutralization of heparin excess in clinical situations, but it does have several drawbacks such as being anticoagulatory itself, when in excess, or at times causing heparin rebound, when at verge of neutralization. In an attempt to find better substitutes for protamine, synthetic polyamino-acids and various types of histone were considered and their activity as heparin antagonists was compared to that of protamine. While protamine was found superior to histones in neutralizing heparin under all the test conditions, poly-DL-lysine showed a wider range of neutralization than did protamine. This particular substance, however, is unsuitable because of its toxicity, and it is recommended to search for additional synthetic polymers. Some of the properties to be desired in a heparin neutralizer are enumerated.