Technical Abstract: Escherichia coli O157:H7 and Salmonella are widely recognized as important agents of food-borne disease with worldwide distribution. The use of ionophores in feeding growing ruminants is widespread in the United States and has attracted recent interest due to the apparent temporal relationship between initial ionophore use and the increase in human E. coli O157:H7 cases. Two experiments were conducted to evaluate the effects of short-term feeding of ionophores on fecal shedding, intestinal concentrations, and antimicrobial susceptibility of E. coli O157:H7 and S. Typhimurium in growing lambs. Sixteen lambs were used in each experiment, four lambs per treatment group: monensin (MON), laidlomycin propionate (LP), bambermycin (BBM) and a control (CON) treatment. Lambs were fed a grain and hay diet with their respective ionophore for 12 days prior to experimental inoculation with a non-toxigenic strain of E. coli O157:H7 or S. Typhimurium. Animals continued on their respective diets an additional 12 days and fecal shedding was monitored daily. Lambs were euthanized and tissues and contents sampled from the rumen, cecum, and rectum. No differences (P > 0.05) in fecal shedding of Salmonella or E. coli were found, although E. coli concentration appeared to decrease more quickly over time in control animals compared with ionophore treated animals. Lumen contents and tissue samples from the rumen, cecum and rectum for Salmonella or E. coli were not different (P > 0.05) among treatments. Feeding MON did decrease (P < .05) the incidence of scours in sheep infected with Salmonella when compared to CON, BBM, and LP treatments. No differences in anti-microbial susceptibility were found in any of the E. coli or Salmonella isolates. These studies found no significant effects of short-term ionophore feeding on E. coli and Salmonella shedding or on anti-microbial susceptibility in experimentally infected lambs.