Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection. In a prospective, double-blind, randomized study, we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients. Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis. Mucositis also resolved more quickly in patients receiving chlorhexidine. Concomitant reductions in total oral streptococci (p less than 0.02-p less than 0.001) and oral candida (p less than 0.004) were seen in patients using chlorhexidine. Persistent clinical oral candidiasis (thrush) was observed in 15 to 27 control group patients (56%), but only transiently in two (8%) of 24 patients who used chlorhexidine rinse (p less than 0.001). Five of 27 control group patients (19%) had candidemia, while no candidemia was observed in the chlorhexidine group (p less than 0.03). Three deaths from disseminated candidiasis occurred in the placebo group; none occurred in patients who received chlorhexidine. Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation. The reductions in mucositis and in oral candida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation.