We treated 69 patients who had hereditary angioedema with danazol to alleviate attacks of mucocutaneous angioedema involving the skin, oropharynx, and gastrointestinal tract, and we documented the continued efficacy of danazol for long-term treatment (1 to 6 years) of hereditary angioedema. Significant dose-related, adverse reactions occurred, including weight gain, myalgias, headaches, microscopic hematuria, abnormal liver function tests, anxiety, altered libido, alopecia, dizziness, and nausea. Alterations in menstrual function were consistently observed. About 10% of patients noted masculinizing side effects, such as acne, hirsutism, and voice deepening. We recommend downward titration of danazol dosage to achieve control of attacks and minimize adverse reactions. Periodic monitoring of patients on long-term danazol therapy is essential to avoid undesirable toxicity.