Fourteen patients with progressive metastatic adrenal cortical carcinoma were treated with a combination of 5-fluorouracil (5-FU), doxorubicin, and cisplatin (FAP). All had a large tumor burden. Six patients had a hormone-producing tumor; mitotane treatment was given to five of them during chemotherapy for its possible antihormonal effects. Treatment could be evaluated in 13 patients. The overall response rate was 23% (95% confidence interval [CI], 5% to 54%). A complete remission, which lasted for 42 months, was achieved in one patient. Partial remissions, which lasted for 6 and 11 months, were achieved in two patients. Cardiotoxicity appeared in three patients, myelotoxicity in four, and nephrotoxicity in one. This confirms that this regimen is an active combination for the treatment of metastatic adrenal cortical carcinoma.