The injection of carrageenan into the rat pleural cavity provoked an intense inflammatory reaction with the formation of an exudate which contained mainly neutrophils but which was also rich in mast cells and histamine. There was, however, no evidence that histamine participated in the reaction. The mast cells remained intact, and no increase in extracellular histamine levels was observed. Prior treatment with bot H1 and H2 histimine receptor antagonists or depletion of the histamine stores by pretreatment with compound 48/80 did not alter the reaction. In contrast, the exudate formed in response to the intrapleural injection of small doses (0.05 mg/kg) of compound 48/80 was reduced by pretreatment with the antihistamine compounds and, unlike the exudate formed after carrageenan injection, was devoid of neutrophils. Since saline washes of the pleural cavity of untreated rats had histamine and mast cell contents similar to those of the exudates of the carrageenan-treated rats, the source of histamine appeared to be mast cells from the pleural cavity.