Mucositis has been a significant debilitating side effect to the treatment of head and neck cancer by irradiation. A change in prophylactic treatment policy was made in August 1991 such that a total of 59 patients was divided into two groups. In Group A, 37 patients were treated prophylactically principally by sucralfate; while in Group B, 22 patients were treated by a three-part prophylactic regimen consisting of sucralfate, either cipriofloxacin or ampicillin, and clotrimazole troches. In Group A patients, unless they had limited fields as for stage 1 vocal cord patients, they uniformly progressed from patchy to confluent or severe mucositis (31/37 severe mucositis). Of the 22 patients in Group B, three patients also arrived at completion of treatment with severe or confluent mucositis; 12 of 22 experienced mild to patchy mucositis by completion, and seven of 22 retained their mucosa entirely intact at the completion of treatment. Four of 22 patients in Group B encountered a clinically diagnosed herpes virus infection of the oropharynx during treatment, which improved when Zovirax was added to their regimen. We conclude that mucositis is clearly and markedly improved by utilization of our prophylactic regimen for Gram-negative rods and fungi.