Chlorhexidine's structural characteristics give it potent antimicrobial activity, effectiveness at low concentrations, substantivity that prolongs its therapeutic effect in the oral environment, minimal resorption from the gastrointestinal tract, and the ability to reduce plaque. The use of this agent for oral stomatitis in neoplasia patients has recently been studied. Treatment-associated oral soft tissue inflammation and ulceration were significantly reduced by chlorhexidine in patients undergoing intensive chemotherapy. Reductions in total streptococci and yeast counts were also observed. When used in conjunction with systemic antifungal agents, such as nystatin or clotrimazole, a significantly decreased incidence of clinical oral candidiasis and Candida septicemia was observed. In contrast, in two studies in which high-dose head and neck radiation therapy was applied, there was no reduction in stomatitis. Oral gram-negative bacilli have been shown to increase in high-dose chemotherapy patients who are taking chlorhexidine during the treatment period (3 wk to 2 mo). However, no increase in systemic gram-negative infections or other adverse negative medical consequences were observed. This agent appears to be of therapeutic benefit in reduction of dental plaque, gingivitis, and stomatitis in the high-risk chemotherapy population when used in conjunction with other topical and systemic antimicrobial agents as prophylaxis. Although no toxic or serious adverse effects of chlorhexidine rinse have been observed in the short-term studies to date, the effects of longer-term chlorhexidine administration should be evaluated.