Five patients with metastatic adrenal cortical carcinoma were treated with a combination of 5-fluorouracil (5-FU), doxorubicin, and cisplatin. All patients had a nonhormone producing tumor. A large tumor burden made them unsuitable for mitotane treatment. Treatment could be evaluated in four patients. A complete remission was achieved in one patient and lasted for 38 months: this patient is still alive and free of disease. Furthermore, a minor response and a disease stabilization also were observed. Cardiotoxicity occurred in one patient and myelosuppression in another patient. This regimen appears to be an active combination for the treatment of metastatic adrenal cortical carcinoma.