In a prospective, randomized study of patients with major burns, the efficacy of cerium nitrate-silver sulfadiazine cream was compared with that of silver sulfadiazine cream alone. Patients (60) were studied in 2 groups with matching mean ages and mean burn sizes. Patients with associated injuries, smoke inhalation or major medical illnesses were excluded from the study. The total number of deaths and the total number of deaths from sepsis were equal in both groups. The total number of patients whose quantitative burn wound biopsies indicated light (102 to 105 organisms/g) or heavy (over 105 organisms/g) colonization by microorganisms was not statistically different between the 2 groups. The distribution of bacterial isolates by organism was similar in both groups. In vitro sensitivity determinations indicated a comparable efficacy between the 2 agents. In this study, no clear-cut superiority of 1 topical agent over the other could be demonstrated.