A 67-year-old man developed non-cardiogenic pulmonary edema after taking a hydrochlorothiazide (HCTZ) tablet. The symptoms remitted following supportive treatment but recurred after rechallenge. Immunologic studies showed increased immunoglobulin E, negative lymphocyte transformation test when exposed to HCTZ, normal blood lymphocyte subpopulations and complement levels, and negative antinuclear antibodies. We reviewed 22 previous reported cases and emphasized that physicians should be aware of this rare but life-threatening reaction.