Early in the use of certain purified dextran solutions as plasma volume expanders in the treatment of shock in man, it was observed that immediate type allergic reactions could be produced (1)(2)(3)(4). The then available clinical dextrans of Swedish and British origin had been found to give a high incidence of allergic reactions, while a product of American manufacture produced a very low incidence (3, 4). The reason for this difference remained obscure.Studies on the antigenicity of purified dextrans showed them to be non-antigenic in the rabbit (5, 6) and guinea pig (6), whereas initial injection in rats gave an unusual type of allergic reaction (7-9) characterized by rapid onset of edema of the paws and snout.Studies by Kabat and Berg (10,11) shown that a significant proportion of individuals showed small amounts of precipitating antibody to dextran (cf. 13) and wheal and erythema type sensitivity before any known deliberate contact with dextran.In view of the interest in dextran solution as a plasma volume expander in the therapy of shock, and since the basis of the systemic reactions to dextran was not understood, and methods of commercial manufacture of dextran solution frequently failed to yield products which did not produce allergic reactions, it became important to evaluate the possible role of existing skin sensitivity and circulating antibody to dextran in relation to systemic reactions to infusions of dextran in a group of normal individuals. A cooperative study sponsored by the Subcommittee on Shock of the National Research Council and the Armed Services was undertaken.' Earlier findings (3, 4) were confirmed that the incidence of generalized allergic reactions varied quite sharply with the type of dextran and manufacturing process used at that time. With a dextran giving a high incidence of systemic allergic reactions on intravenous infusion, a high statistical correlation was found between allergic reactions and initial skin sensitivity to certain native dextrans and also between allergic reactions and initial circulating precipitin levels as determined with certain dextrans. Clinical dextrans gave a low incidence of positive skin test reactions, whereas native dextrans gave a high incidence of positive reactions. Hehre and Neill (cited in Reference 2) had noted some positive skin reactions to native dextran in man.A correlation between the incidence of skin sensitivity and the structure of the native dextran was also found. From an interpretation of the 1160