OBJECTIVE To examine the efficacy of fast neutron radiotherapy for the treatment of patients with locally advanced, adenoid cystic carcinoma of minor salivary glands and to identify prognostic variables associated with local control, overall survival, and cause specific survival. METHODS Eighty-four patients having adenoid cystic carcinoma of minor salivary glands were treated with fast neutron radiotherapy during the years 1985-1994. All patients had either unresectable disease or gross disease remaining after attempted surgical extirpation. Seventeen patients had previously received conventional radiotherapy and their subsequent treatment fields and doses for neutron radiotherapy were modified for critical sites (brainstem, spinal cord, brain). Although the median doses (tumor maximum and tumor minimum) only varied by < or = 10%, treatment portals were substantially smaller in these patients because of normal tissue complication considerations. Twelve patients (13%) had distant metastases at the time of treatment and were only treated palliatively with smaller treatment portals and lower median tumor doses (< or = 80% of the doses delivered to curatively treated patients). Seventy-two patients were treated with curative intent, with nine of these having recurrent tumors after prior full-dose radiotherapy. The median duration of follow-up at the time of analysis was 31.5 months (range 3-115). Sites of disease and number of patients treated per disease site were as follows: paranasal sinus-31; oral cavity-20; oropharynx-12; nasopharynx-11; trachea-6; and other sites in the head and neck-4. RESULTS The 5-year actuarial local-regional tumor control rate for all patients treated with curative intent was 47%. Patients without involvement of the cavernous sinus, base of skull, or nasopharynx (51 patients) had a 5-year actuarial local-regional control rate of 59%, whereas local-regional control was significantly lower (15%) for patients with tumors involving these sites (p < 0.005). In the latter cases, normal tissue injury considerations precluded delivery of the full dose to the entire tumor. Patients with no history of prior radiotherapy (63 patients) had an actuarial local control rate of 57% at 5 years compared to 18% for those (9 patients) who had been previously irradiated with conventional photons (p = 0.018). Eliminating the dose-limiting factors of prior radiation therapy and/or high risk sites of involvement, the 5-year actuarial local-regional control rate for these 46 patients was 63%, with an actuarial cause specific survival rate of 79%. Lymph node status was a predictor of distant metastasis: 57% of node positive patients developed distant metastases by 5 years compared to 15% of patients with negative nodes (p < 0.0005), and patients who had nodal involvement developed distant metastases sooner than node negative patients (p < 0.0001). The 5-year actuarial overall survival and cause specific survival for the 72 patients treated with curative intent were 59% and 64%, respectively. CONCLUSIONS Fast neutron radiotherapy offers high local-regional control and survival rates for patients with locally advanced, unresectable adenoid cystic carcinomas of minor salivary glands. It should be considered as initial primary treatment for these patients, as well as for other patients in whom surgical extirpation would cause considerable morbidity.