The National Institutes of Health recently recommended research initiatives to investigate oral complications of cancer chemotherapy. This prospective cohort study investigated orofacial complications of combination chemotherapy (cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in women with breast cancer. Thirty-four patients were given baseline interviews and examinations. Each patient was given weekly orofacial examinations and biweekly interviews for the first seven cycles of cytotoxic treatment. The orofacial complications included neurotoxicity caused by vincristine, mucositis, and candidiasis. Neurotoxicity affected 22 of 34 (65%) patients, was significantly associated with age less than 50 years (p less than 0.05), and manifested as pain in 19 of 34 (56%) patients. Mucositis affected 7 of 34 (21%) patients and was significantly associated with the occurrence of lesions of the oral mucosa at baseline examination; and smaller body surface area--indicating a dose-related toxicity (p less than 0.05). In four of the patients with mucositis (57%) granulocytopenia developed during the 7 days after the onset of mucositis. Intraoral candidiasis affected 4 of 34 (12%) patients.