The impact of prophylaxis with 400 mg/day fluconazole on fungal colonization at different body sites was assessed in a randomized, double-blind, placebo controlled study among patients with leukaemia and those undergoing bone marrow transplantation. The study drug was given throughout the period of neutropenia and samples were obtained at weekly intervals. Of the 23 patients in each group, 11 of those given fluconazole and 12 placebo recipients were colonized at entry. The commonest sites were the oropharynx and rectum and Candida albicans was the most frequent isolate. Fluconazole led to a marked reduction in colonization by the second week of treatment to 29% compared with 68% for those given the placebo. Two-weeks after stopping the study regimen there was little change with yeast being isolated from 33% and 81% respectively. Fluconazole was particularly effective in reducing the carriage of C. albicans in the oropharynx from 46% to 0-10% and in maintaining this throughout prophylaxis. Recovery of Candida (Torulopsis) glabrata from the perianal region steadily increased to around 30% in both patient groups and while Candida krusei species were found exclusively in patients given fluconazole, other candida were more common in the placebo group. These results demonstrate that by rapidly reducing the colonization of the alimentary tract, fluconazole eliminates the major reservoir for infection with yeasts other than C. glabrata and C. krusei during the critical period of neutropenia.