This study evaluated the effects of broad-spectrum antibiotics on the gastrointestinal (G.I.) yeast flora of humans and correlated the findings with those obtained from a mouse model of G.I. colonization by Candida albicans. We prospectively studied 46 adult cancer patients who received one of five broad-spectrum antibiotics (ceftriaxone, ceftazidime, ticarcillin-clavulanic acid, imipenem-cilastatin, and aztreonam) as therapy for infections. Quantitative examination of yeast colonization of stools was conducted at the baseline, at the end of antibiotic treatment, and 1 week after discontinuation of therapy. Antibiotics with anaerobic activity (ticarcillin-clavulanic acid) or high G.I. concentrations (ceftriaxone) caused a higher and more sustained increase in G.I. colonization by yeasts than did antibiotics with poor anaerobic activity (ceftazidime and aztreonam) or a low G.I. concentration (imipenem-cilastatin). These results were similar to those obtained with a mouse model of G.I. colonization by C. albicans that involved the same antibiotics. Hence, the mouse model may be useful for evaluation of yeast colonization of the human G.I. tract.