Seventeen patients with advanced or recurrent salivary gland cancer were treated with cisplatin, doxorubicin, and 5-fluorouracil combination chemotherapy (PAF). Two patients achieved a complete response and four patients achieved a partial response, for an overall response rate of 35%. Six of the nine patients who received PAF in the neoadjuvant setting did not respond and proceeded to surgery and/or radiation therapy. No difference in response rate was found between those patients treated for recurrent disease v those treated with neoadjuvant chemotherapy. All three patients with adenocarcinoma responded. The response duration in patients with metastatic or recurrent disease ranged from 6 to 15 months. The PAF regimen was delivered primarily in the outpatient setting and was associated with acceptable toxicity. PAF demonstrates activity in salivary gland malignancies, and further evaluation of this combination seems warranted.