A sequential 37-step pathway scheme has been devised that describes the actions and events responsible for the onset, development, and decay of carrageenan pleurisy. It is postulated that the subpleural cytotoxicity of absorbed carrageenan initiates the response by producing a biphasic subpleural inflammation, the first phase of which precedes any sign of pleural exudation. Pleural exudation began 1 h after the injection of carrageenan and consisted of mobilized neutrophils and a barely detectable exudate volume. The time course of intrapleural neutrophil mobilization was monophasic (S shaped). Monocyte mobilization began after neutrophil mobilization and was also monophasic. Pleural exudate formation was biphasic. The first exudative phase was sensitive to inhibitors of neutrophil mobilization and arachidonate acid cyclooxygenase (AACO). Drug studies revealed that although neutrophils were required to initiate the first exudative process, the cells of the pleura produced a postulated reactive prostaglandin intermediate that increased vascular permeability and resulted in exudate formation. The etiology of the second exudative phase is unknown. This phase is insensitive to AACO inhibitors but is highly sensitive to steroids. Inhibition of monocyte mobilization by colchicine revealed that these were not associated with any exudate formation. Monocytes are postulated to stop the exudative process. These cells phagocytose the mobilized neutrophils and return the pleural cavity to normal. Thus, in this model of acute inflammation, monocytic function is related solely to anti-inflammatory activities.