We conducted a double-blind, placebo-controlled, randomized trial to evaluate the efficacy and safety of tetrachlorodecaoxide (TCDO) in patients with chemotherapy-induced mucositis. Sixty-two patients with World Health Organization grade II-IV oral mucositis were eligible for the study. They were randomized to receive TCDO or placebo, 10 ml, twice daily, swish and swallow, for 7 days. Patients were evaluated for oral pain, dysphagia, and oral intake. Downgrading and total duration of mucositis were documented. Thirty-two were randomized to receive TCDO. Thirty received the placebo. All were evaluable. Both arms were well matched for age, gender, type of underlying neoplasm, and prior history of oral mucositis. Intensity of initial symptoms, degree of mucositis, and time period between delivery of chemotherapy and development of mucositis were also similar. Post-therapy evaluation revealed no significant difference in the mean grade of oral and esophageal pain, or dysphagia between TCDO and placebo. Downgrading or total duration of mucositis did not differ between the two groups. Oral intake improved significantly in patients taking TCDO. Time to subjective improvement in oral pain was significantly shorter with TCDO (3.1 versus 3.6 days). Evaluation on day 3 revealed that 77% of those receiving TCDO were free of oral pain in comparison to 46% receiving placebo (P = 0.05). These results indicate that TCDO may be helpful in palliating some of the symptoms related to oral mucositis. The therapeutic benefit, however, is small and needs to be confirmed in a larger trial.