A randomized evaluation of the effectiveness and toxicity of the combination of doxorubicin and cisplatin and of doxorubicin alone in patients with advanced thyroid carcinoma was carried out. Ninety-two patients were entered and 84 were evaluable. They were stratified according to histological classification, Eastern Cooperative Oncology Group (ECOG) performance status, and metastatic sites. Forty-one patients received doxorubicin as a single agent and seven had partial response (17%). Forty-three patients received the combination, and there were five complete and six partial responses (combined response rate of 26%). This difference for overall response rate is not significant (P greater than 0.1). However, five complete responses were seen in the combination-treatment group, whereas none were observed in the single-agent treatment group; a significant difference was obtained (P = 0.03). Four of these five complete responders survived for more than 2 years, and two patients remained in a complete response after the discontinuation of therapy and are still alive. None of the partial responses exceeded 2 years in duration. The life-threatening toxicities from chemotherapy occurred in five patients treated with the combination of drugs and two treated with doxorubicin alone. However, none of the toxicities were fatal. The study has shown clearly that the quality of response achieved by the combination of drugs is far superior to that achieved by single-agent chemotherapy.