Our analysis of events in immediate hypersensitivity focuses on human and animal models of allergic responses, mechanisms of mediator action, and pharmacologic approaches to allergic diseases. The areas under investigation include asthma, allergic rhinitis, anaphylaxis, urticaria, and mastocytosis. Employing monoclonal antibodies direced at cyclic GMP, the pattern of cells in guinea pig lung responding to histamine stimulation has been identified. Histamine causes alveolar cells, endothelial cells, epithelial cells, and macrophages to devlop increased cyclic GMP. By contrast, atrionatriuretic factor causes smooth muscle cells to also increase their cyclic GMP. Ketotifen has been found to prevent histamine release from mast cells in patients with physical urticarias. Histamine levels in plasma are diagnostic of systemic mastocytosis if consistently elevated. The mechanisms for progesterone-related anaphylaxis has been examined and remains unclear while a third progesterone-sensitive subject with anaphylasis responded to LHRH analogue therapy. Microvascular permeability in skin is increased by histamine, serotonin, and bradykinin, but does not appear to contribute to the edema seen in late phase responses. Plasma hisatmine from patients in gram negative sepsis and shock is reduced below normal. BAL fluids obtained from asthma patients have normal histamine while interstial pulmonary fibrosis is associated with elevated histamine. Neurogenic sensory stimulation leads to increased vascular permeability and mast cell degranulation. Human neutrophils release a factor which induces histamine release from RBL, human basophils, and guinea pig cutaneous mast cells. Rat lung has substance P receptors in the central airways which cause increased vascular permeablity when stimulated.