The acute phase reaction is initiated and regulated by leukocytic pyrogen which is released by activated host phagocytes at inflammatory sites during inflammatory reactions of any etiology. The physiological alterations which follow include, in addition to the characteristic acute phase protein changes, fever, granulocytosis, fall in serum iron and zinc, metabolic stimulation of blood granulocytes, activation of T-cell function and doubtless other effects as yet unrecognized. These responses are mediated by free or by protein-bound LP molecules and reflect both direct receptor coupled effects and more indirect mechanisms such as release of secondary mediators from cells or body fluids and involvement of neural or neurohumoral pathways. This unitarian hypothesis implies a functional interrelationship between the component parts, and allows a model for critical examination and new hypothesis testing. The wider availability of pure preparations of LP and of possible subtypes of LP and of a sensitive immunoassay would help us to prove or to expand this hypothesis and to advance our understanding of this important phase of acute inflammation. Earlier in this conference we heard that the mediator derepresses a message: I'd like to put forward the idea that in the acute phase reaction the mediator is the message.