Mucocutaneous candidiasis caused by Candida albicans is a common complication of human immunodeficiency virus (HIV) infection. Recent reports of isolation of resistant strains of C. albicans raise the specter of more widespread resistance, but limited series are available to analyze situations in which the likelihood of resistance is greatest. We present our experience with fluconazole-resistant candidiasis in patients with HIV infection obtained from retrospective chart review and by testing strains of C. albicans isolated during relapse for susceptibility to antifungal agents. The possible reasons for failure of antifungal therapy are discussed, as well the correlation between in vivo and in vitro data. Resistant candidiasis in patients with HIV disease is an emerging problem of considerable concern that merits further study.