Patients undergoing cytotoxic chemotherapy and radiation therapy often experience severe oral complications during and after treatment despite supervised oral hygiene and conventional antimicrobial regimens. The antimicrobial compound chlorhexidine is an effective topical prophylactic agent against oral mucositis and candidiasis. Oral mucositis developed in four patients who underwent bone marrow transplantation; the condition was severe enough to prompt use of chlorhexidine. In each case, there was clinical resolution of mucositis and a concomitant decrease in the oral microbial burden 1 week after chlorhexidine use began. This strongly suggests that, in addition to its value in protecting these severely immunocompromised patients from oral infection, chlorhexidine also offers a therapeutic benefit in the resolution of existing oral infections and of mucositis.