In the perioperative period, histamine release was shown in numerous situations and pathological states. They include diseases or complications of diseases, preparation and premedication of patients, induction of anaesthesia, maintenance of anaesthesia and surgery, and administration of drugs and treatment in the immediate postoperative period. A premedication with histamine H1 and H2 receptor antagonists was developed which in five controlled clinical trials blocked histamine-release responses of all grades of severity. These included single spots of erythema or a wheal up to life-threatening reactions or even death of the patient or laboratory animal. The necessity for a new premedication was investigated by methods of medical decision-making considering the incidence of the reactions, classification of severity, efficiency of prophylaxis and treatment of anaphylactoid reactions, and side-effects. As a result, the premedication with dimethpyrindene (Forhistal,® Fenistil®) plus cimetidine (Tagamet®) was recommended in a series of patients at risk: those with a history of hypersensitivity reactions to intravenous agents or atopy, patients with a second I.V. drug exposure within a few days, those undergoing surgery with a high risk of histamine release, patients of > 70 years age, and poor-risk patients with preoperative cardiac, respiratory or liver insufficiency and shock.