The present study investigated the prophylactic efficacy of fluconazole at 100-200 mg/day against invasive fungal infections during bone marrow transplantation (BMT). During July 1990 to December 1991, all BMT recipients received antifungal prophylaxis with fluconazole at either 200 mg/day or 100 mg/day. Historical controls were those that received no antifungal prophylaxis (January 1989 to June 1990). Fungemia occurred in 4 of 112 fluconazole recipients and 8 of 79 controls (p < 0.05) prior to engraftment. Torulopsis (Candida) glabrata (three patients), Cryptococcus terreus and Candida tropicalis (mixed in one patient) caused fungemia in four patients in the fluconazole group; Candida albicans caused six of eight fungemic episodes in the controls. All three Torulopsis glabrata isolates were fluconazole-resistant. Colonization due to C. albicans was markedly diminished in the fluconazole group (19 of 112 patients versus 53 of 79 controls). T. glabrata, on the other hand, was a more common colonizing organism in the fluconazole group (36 of 112 vs 10 of 79). The frequency of isolating C. albicans and/or T. glabrata was significantly different between fluconazole and control groups (p < 0.0001). Empiric use of amphotericin B therapy was markedly reduced in the fluconazole group (4.5% vs 34%; p < 0.0001). Fluconazole at 200 mg/day or 100 mg/day appeared equally effective. Fluconazole at a daily dose of 100 mg or 200 mg as antifungal prophylaxis during BMT: (1) significantly reduced the frequency of systemic fungal infections, (2) markedly reduced colonization and infection due to C. albicans, and (3) markedly reduced the need for empiric amphotericin B therapy.(ABSTRACT TRUNCATED AT 250 WORDS)