A 40-year-old woman had monthly episodes of angioedema, eruption of pruritic papules and plaques and fever. During acute episodes white blood cell counts increased to 31,000/mm3 with 75% eosinophils, body weight increased to 10% of baseline weight, and urine excretion decreased to 40 ml/24 hours. No evidence was found for cardiac or other visceral organ involvement. Extensive diagnostic evaluations revealed no evidence for parasitic infestation, connective tissue disease, or neoplastic disorders. Results of immunologic studies revealed increased serum IgM and IgE levels and showed elevated levels of circulating activated T-helper cells. Biopsy specimens of lesional skin showed dermal infiltration of lymphocytes and eosinophils with deposition of eosinophil granule major basic protein in the extracellular matrix within the dermis. Immunophenotyping of the dermal infiltrate with monoclonal antibodies revealed the predominance of T-helper cells, many of them expressing the human leukocyte antigen (HLA)-DR, suggesting that angioedema with eosinophilia may be a T-helper cell-mediated disease.