The frequency of rectal infections is increased in patients with acute leukemia. Complications associated with rectal lesions may be severe enough to cause life-threatening septicemia. Clinical research evaluating the effects of preventive perirectal skin care is scarce. This study's purpose was to determine whether using chlorhexidine digluconate in a prophylactic perirectal skin-care regimen decreases perirectal infections and whether it produces more skin irritation than a nonmedicated skin cleanser. The sample consisted of 40 patients, 16 of whom were randomized to use chlorhexidine digluconate and 24 of whom were randomized to use nonmedicated skin cleanser. Chi-square and t-tests were used to analyze the incidence of skin breakdown and rectal infections; the correlation between the two factors; a positive history of rectal infections, fissures, or hemorrhoids; presence of hemorrhoids; severity of diarrhea; and duration and severity of granulocytopenia. A positive relationship was found between the severity of granulocytopenia and the incidence of rectal infections (p = 0.02). No significant difference was seen in the occurrence of perirectal infections (p = 0.35) or skin breakdown (p = 0.18) between the two groups. The data suggest that CHG does not offer increased protection against perirectal infections in patients undergoing intensive chemotherapy, nor is it more irritating than a nonmedicated skin cleanser. Further studies are needed to examine the efficacy of hygienic measures such as using skin disinfectants to prevent infections in patients who are immunocompromised.