Pieroni, Robert E. (Massachusetts Department of Public Health, Boston), Edward J. Broderick, and Leo Levine. Endotoxin-induced hypersensitivity to histamine in mice. I. Contrasting effects of bacterial lipopolysaccharides and the classical histamine-sensitizing factor of Bordetella pertussis. J. Bacteriol. 91:2169–2174. 1966.—The capacity of typhoid and possibly of pertussis endotoxins to induce histamine-shock susceptibility in some of the mice that survive graded doses of these endotoxins was confirmed. It was demonstrated, however, that pertussis endotoxin cannot be the main source of the typical histamine sensitization of pertussis vaccine. The following points are made. (i) With typhoid and pertussis endotoxins as inducers of histamine shock, no systematic relation between deaths and induction dose could be found, and 100% mortality could not be achieved. In contrast, with pertussis protective fraction as inducer, there was clear dose-response regression, with 100% mortality possible. (ii) The major part of the histamine-sensitizing activity of pertussis vaccine or its extracts was destroyed by trypsinization or by heating for 30 min at 100 C. These processes do not affect the histamine-sensitizing activity of the endotoxins. The implication for purified pertussis vaccine with high histamine-sensitization capacity is that endotoxin need not necessarily be present. The significance and possible mechanisms of action of endotoxin-induced histamine sensitivity are briefly discussed.