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Phosphatidic acids (PAs) are a molecularly diverse group of phospholipids. Certain species of PA are highly active intracellular signaling molecules associated with cellular activation and mitogenesis. Not surprisingly, the PA species active in signaling are not produced by normal cells under homeostatic conditions. Recently the molecular species of PA associated with specific cellular activating events have been identified and compounds that inhibit the formation of specific PA species have been synthesised. We have characterised four classes of PA not derived from phosphatidylinositol hydrolysis that are involved in intracellularsignaling. PA1α is produced following exposure of cells to lipopolysaccharide, IL-1, hypoxia-reoxygenation, IL-8, or platelet activating factor. Lisofylline, a functional inhibitor of PA1a formation, is in Phase II-III trials as a therapeutic to reduce toxicities of anti-cancer therapies and for cytokine-mediated acute systemic inflammatory conditions. PA1α, PA1β and PA2 are pro...