Because of the scarcity of such lesions, little is known about the efficacy of chemotherapy for advanced salivary gland cancers. Although surgery and irradiation are the mainstays of treatment, patients with recurrent tumors and those with unresectable or metastatic cancer are not candidates for this usual approach. Ten patients with recurrent, metastatic, or unresectable salivary gland tumors were treated with combination chemotherapy, primarily with cisplatin, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide, or cisplatin with 5-fluorouracil. In patients whose tumors exhibited no response, second-line drugs were used. The overall response rate was 50%--with one complete response--but the duration of response was short. This report contributes to the growing data base that demonstrates definite chemosensitivity of these tumors. To date, 116 patients have been reviewed. Adenocarcinoma-like cancers respond best to cisplatin, doxorubicin hydrochloride, and 5-fluorouracil. High-grade mucoepidermoid carcinoma may show a sensitivity similar to that of squamous cell carcinoma. Multi-institutional protocols need to be developed to assess the roles of adjuvant and palliative chemotherapy in the treatment of salivary gland cancer.