We have developed a model of IgE-dependent, mast cell–mediated arthritis in rats. One knee joint (test joint) of a Sprague-Dawley rat was injected with 1 μg of a monoclonal IgE specific for dinitrophenol, and the contralateral (control) joint was injected with the same amount of an irrelevant monoclonal IgE in phosphate buffered saline or with phosphate buffered saline alone. Within 5 minutes of intravenous injection of antigen, an acute, transient arthritis occurred in the test joints only, with swelling and extravasation of intravascular blue dye and 125I-labeled albumin, decreased numbers of stainable mast cells, and decreased histamine content of the joint synovium. Pretreatment of experimental animals with H1 and H2 antihistamines did not completely block the reaction. These data show that IgE-dependent synovial mast cell degranulation causes a transient, nondestructive arthritis, reminiscent of lupus arthritis and intermittent hydrarthrosis.