Four broad-spectrum antibiotics — azlocillin, mezlocillin, cefuroxime, and moxalactam-were injected subcutaneously into mice twice a day. The animals were divided into treatment groups for each antibiotic and then into subgroups, each subgroup receiving a different dose of antibiotic. The effect of treatment on the resistance of the digestive tract to colonization and the effect of treatment on endogenous gram-negative and intestinal streptococcal flora were studied: resistance to colonization decreased during treatment with ∼0.9 mg of antibiotic per mouse per day. During treatment with this dose or a higher dose, Escherichia coli or a strain of Enterobacter resistant to the antibiotic being used grew to significantly higher numbers per gram of feces than in the control groups. The resistance of the digestive tract to colonization in mice decreases during systemic treatment with all four antibiotics at or above certain dose levels, a result also likely to occur in humans.