Hypersensitivity reactions to intravenous macromolecular solutions are an exacerbation of the organism defence mechanisms with production of exaggerated and deleterious effects. The immediate adverse reactions to drugs (anaphylaxis) have clinical manifestations-due to histamine release principally: cutaneous (rash, urticaria, edema); pulmonary (bronchospasm), and cardiovascular (hypotension, collapse, cardiac arrest); their intensity may be graded in degrees I to V. These reactions may be either truly anaphylactic (immunological): hypersensitivity type I with reaginic antibodies (IgE), requiring previous exposure to the drug (true allergy); other immune responses with antigen-antibody (IgG or IgM) complexes activating classical complement pathway; or anaphylactoid; indirect histamine release by direct activation of C3 (alternate complement pathway) direct histamine release by pharmacological effect; dose related effects. The incidence of reactions to plasma substitutes vary greatly according to authors. In most cases, gelatin derivatives act by direct action on mast cells (histamine release) and indeed prevention of reaction with antihistamines is effective; antibody related reactions occasionally occur (immune complexes). With dextrans, soluble immune complexes aggregates have been described; dextrans may react to specific antibodies (possibly previously produced by bacterial polysaccharides); complement activation occur only in severe reactions. HES is comparable to dextran, antibodies have been described. Other factors may predispose to anaphylactoid reactions such as genetic factors (atopy, primary complement anomalies) underlying immune processes and stress. All macromolecular solutions carry the risk of anaphylactoid side-reactions, the mechanisms of which are not completely clarified.