Oral mucositis is a dose-limiting toxicity of 5-fluorouracil (5-FU). This prospective cohort study investigated factors associated with mucositis in patients receiving 5-FU for cancer of the digestive tract. Sixty-three patients (mean age 65 years) completed self-administered questionnaires and had interviews, oral examinations and unstimulated whole salivary flow measurements at baseline and follow-up appointments. The duration of follow-up was 2 months. Predictor variables included sociodemographic data, body surface area, diabetes, smoking, alcohol consumption, salivary flow, oral hygiene, presence of prostheses, performance status, regimen of cytotoxic drugs, hematological data, and herpes simplex virus antibody titer. Forty-six per cent of patients developed at least one episode of oral mucositis during cytotoxic treatment. Pearson's chi-square analysis showed that mucositis was significantly associated with xerostomia at baseline, xerostomia during chemotherapy, and lower baseline neutrophil counts (P < or = 0.05). Multiple logistic regression analysis indicated that xerostomia at baseline (odds ratio, OR = 10.0), or baseline neutrophil level under 4000 cells/mm3 (OR = 3.9) were significant predictors of mucositis. Taking into account the effect of neutrophil level at baseline, xerostomia during chemotherapy (OR = 4.5) was also a significant predictor of mucositis. The results showed that xerostomia and lower baseline neutrophil levels are significantly associated with oral mucositis. These variables should be taken into consideration in the design of intervention studies to reduce the frequency and severity of mucositis. More research is required to investigate the role of saliva and neutrophils in the pathogenesis of chemotherapy-induced mucositis.