The aim of the present study was to investigate the incidence of Candida stomatitis and resulting interruptions in radiation and radiochemotherapy in 50 patients suffering from squamous cell carcinomas of the head and neck region receiving fluconazole (100 mg d-1) in comparison with a historical control group (n = 50) without specific prophylaxis. Twenty of the control patients (40%) demonstrated Candida stomatitis, with seven of them (14%) requiring interruptions in anticancer therapy. In contrast, none of the patients with fluconazole had evidence of Candida stomatitis (P = 0.0000051) and subsequent interruption of anti-cancer therapy (P = 0.0061). Laboratory monitoring for the presence of Candida species was performed in 30 patients before and after therapy with fluconazole. Candida albicans was identified less frequently after therapy when compared with the pretreatment status. However, C. glabrata and C. krusei were isolated in some of the patients, probably because of drug resistance of these subspecies. The results demonstrate the clinical usefulness of prophylactic fluconazole applications in patients suffering from head and neck tumours with the aim of reducing Candida stomatitis and the resulting interruptions in radiation and radiochemotherapy.