Technical Abstract: Previous research conducted by our laboratory investigated the incidence of multi-drug resistant (MDR) Salmonella in dairy cattle and reported that individual cattle, and most often calves, shed multiple Salmonella serotypes that vary in the degree of antibiotic resistance. More recently, we investigated the high incidence of an MDR E. coli in dairy calves and found that it disappears with increasing age. Taken together, this suggests the MDR E. coli population may be an important reservoir for resistance elements that could potentially transfer to Salmonella. Therefore, the objective of the current research was to determine if resistance transfers from MDR E. coli to susceptible strains of Salmonella (Experiment I) and to examine the effect of modifying the rumen microbial ecosystem on resistance transfer (Experiment II). Both experiments utilized Holstein calves (approx. 3 weeks old) naturally colonized with MDR E. coli and fecal culture negative for Salmonella. Fecal samples were collected for culture of Salmonella and MDR E. coli throughout both experiments following experimental inoculation with the susceptible Salmonella strains. Results from Experiment I suggest that resistance did transfer from the MDR E. coli to the inoculated strains of Salmonella, with these strains demonstrating multiple antibiotic resistance following in vivo exposure to MDR E. coli. However, serogrouping and serotyping results of a portion of the Salmonella isolates recovered from the calves indicated two new strains of Salmonella, confounding interpretation of the results. In the second experiment, all fecal samples in all treatments were Salmonella negative when plated on antibiotic-supplemented media, indicating that resistance did not transfer to the inoculated Salmonella under these experimental conditions. These results suggest that antimicrobial resistance can transfer from MDR E. coli to Salmonella in vivo, however further research confirming these results is warranted.