Male ICR Swiss mice (2 to 3 months old) were fed Candida albicans in their drinking water for 3 days, followed by no treatment, antibiotics in their drinking water (daily), or immunosuppressants given by intraperitoneal injection (two to three times weekly) over a 3- to 4-week period. The organs of animals were processed to determine the numbers of C. albicans and total aerobic bacteria per g of tissue. Untreated animals had mean Candida counts during the 1-month period of 10(2.3) CFU/g of cecum. Animals in six of eight antibiotic-treated groups had mean cecal Candida counts higher than those of control animals (P less than 0.05), with clindamycin-gentamicin producing the highest counts (10(4.7) CFU/g). Cyclophosphamide produced counts (10(4.3) CFU/g) which were higher (P less than 0.05) than those resulting from methotrexate (10(3.0) CFU/g) or steroid (10(2.7) CFU/g) treatment. Cyclophosphamide-clindamycin-gentamicin treatment was associated with the highest (P less than 0.05) levels of Candida colonization (10(6.5) CFU/g). Mice receiving immunosuppressants plus clindamycin-gentamicin were more likely to disseminate C. albicans than were mice receiving antibiotics alone (P less than 0.001). Our findings suggest that colonization of the guts of mice by C. albicans can be facilitated by manipulating the aerobic, anaerobic, or both types of gut flora. The combined effect of immunosuppressants on both Candida gut colonization and dissemination appears multifactorial and deserves further investigation.