Protamine hypersensitivity has been documented by intra-dermal skin testing in three patients who demonstrated sudden cardiovascular collapse and bronchospasm following the use of intravenous protamine sulphate. All patients had been given protamine previously. The effects of the anaphylactic response were terminated quickly by the administration of intravenous adrenaline associated with plasma volume expansion. Intra-dermal skin testing against all anaesthetic agents is recommended so that the specific allergen can be identified. In patients who are shown to be allergic to protamine sulphate and who require cardiac or vascular surgery careful monitoring of heparin dosage and neutralisation with hexadimethrine (Polybrene) intravenously appears to be a safe alternative.