(1) Histamine release in man could be demonstrated using the fluorometric histamine assay in plasma as a reliable test. (2) Histamine release in animals may be relevant in some cases for human subjects, as shown for anaesthetic drugs and plasma substitutes on gelatin basis. In other cases histamine release in animals may not be relevant for man as demonstrated for dextran. (3) Even if a small histamine release could be detected in human subjects as in the case of dextran this must not implicate that also in severe anaphylactoid incidents histamine release is the cause of these events. (4) Plasma histamine determinations led to a much better understanding of histamine-induced reactions in human subjects than other techniques and — which is the most important advantage — increase the possibility to differentiate between histamine-induced reactions and anaphylactoid reactions caused by other mediators. The suggestion in former time that histamine might be involved in all types of ‘allergic’ reactions induced a histamine philosophy. Differentiation, however, gives histamine its place at least in human pathophysiology.