Histamine-release responses in clinical conditionsshow a wide range of severity, from a single spot of erythema or a wheal up to a life-threatening reaction or the death of the patient.To demonstrate the efficiency of Hi-and HE-blockade in preventing histamine-induced anaphylactic and anaphylactoid reactions, a series of controlled trials was carried out in patients, volunteers and dogs presenting histamine-release responses of all three grades of severity (table I). Both the histamine-releasing drugs and the histamine H1-and HE-receptor antagonists had to be chosen for these trials according to a series of well-conceived and strict criteria.For the histamine H1-and HE-receptor antagonists, the criteria for selection included potency, selectivity, duration of action, clinical experience with the drug and the availability both for tlae oral and the intravenous routes. For the HE-receptor antagonist, selection was not difficult since, at the time of the first trials, cimetidine was the only available drug on the market. However, the choice of the Hi-receptor antagonist was very difficult.