The mast cell is widely thought to contribute importantly to the cardiopulmonary changes associated with anaphylaxis, but much of the evidence for this is indirect. We, therefore, performed a detailed assessment of heart rate and pulmonary function during active anaphylaxis in genetically mast cell-deficient W/Wv or S1/S1d mice, the congenic normal (+/+) mice, and W/Wv mice repaired of their mast cell deficiency by transplantation of bone marrow from the congenic +/+ mice (+/+ BM-->W/Wv mice). For all five groups of mice, Ag challenge resulted in the death of more than two-thirds of the sensitized animals, whereas none of the nonsensitized control mice died as a result of Ag infusion. Sensitized normal (WBB6F1(-)+/+ or WCB6F1(-)+/+) mice and +/+BM-->W/Wv mice developed increases in heart rate that were significantly greater than those of nonsensitized +/+ mice or those of sensitized mast cell-deficient mice, indicating that mast cells contribute to the tachycardia observed in this form of active anaphylaxis. By contrast, even though some of the pulmonary changes associated with active anaphylaxis were more severe in +/+ than in mast cell-deficient mice, it was not clear to what extent this difference was mast cell dependent. W/Wv mice undergoing active anaphylaxis developed decreases in systemic arterial blood pressure that occurred more rapidly and were more severe than those observed in the congenic +/+ mice, indicating that the hypotension associated with this model of anaphylaxis also can occur by mast cell-independent mechanisms. We conclude that in this model of anaphylaxis mast cells: 1) are required for the development of the tachycardia response; 2) may contribute to, but are not essential for, production of decreases in lung function; and 3) are not necessary for the development of hypotension or death.