There is increasing evidence that histamine may have wider proinflammatory and immunomodulatory activities than previously reported. It may influence several functions of lymphocytes, monocytes, basophils and macrophages, modulating the release of inflammatory mediators and cytokines. These observations have aroused interest in the pharmacology and clinical applications of histamine H1 receptor antagonists and have led to the identification of novel antiinflammatory properties for this class of drugs. Oxatomide, initially characterized as an H1 antagonist, inhibits the secretion of several mediators of inflammation from human basophils and mast cells. In vitro oxatomide inhibits the release of both preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C4 and prostaglandin D2). The inhibitory effect is not restricted to basophils and mast cells but is also evident on other inflammatory cells such as the neutrophils. In this cell, oxatomide inhibits arachidonic acid mobilization, and leukotriene B4 and platelet-activating factor synthesis, presumably by reducing the activity of cytosolic phospholipase A2. These observations extend the pharmacological activities of oxatomide beyond H1 receptor antagonism and suggest that this drug influences a variety of biochemical events in human inflammatory cells. These antiinflammatory activities help to explain its beneficial effect in various allergic and inflammatory disorders, including urticaria, allergic rhinitis and bronchial asthma.