Anaphylaxis due to intravascular interaction of hyperimmune antibody with antigen was studied in rabbits, swine and rats. Obstruction of the pulmonary vessels by the immune precipitates was found to initiate the process. This is followed by aggregation of PMN-leucocytes and platelets in pulmonary vessels and phagocytosis of the precipitates by these blood elements. During this process degranulation of the cells takes place with release of lysosomal contents. As a concomitant a rise in plasma acid protease and other hydrolases was demonstrated, presumably derived from the degranulating PMN-leucocytes and platelets. Unlike leukopaenic animals, normal ones showed a more marked hypotension, a greater tendency to protracted shock and developed focal and confluent haemorrhagic pulmonary lesions. It is suggested that anaphylaxis due to intravascular antigen—antibody interaction or aggregate anaphylaxis is a systemic or pulmonary Arthus reaction, rather than a `true' anaphylaxis.