Adrenal cortical carcinoma is a rare tumor with a poor prognosis. Experience with chemotherapy in this tumor besides mitotane is practically nonexistent. We are reporting the results of 27 trials of various chemotherapeutic regimens among 12 patients with metastatic disease. Most patients (nine of 12) had a trial of mitotane before cytotoxic drugs were instituted. Three patients achieved a partial remission, one achieved a minor regression, and three had stable disease. All of the responses were of short duration. Alkylating agents and doxorubicin appear to have some antitumor activity. Multi-institutional cooperative studies are needed to detect active drugs and drug combinations against this neoplasm.