One-day-old leghorn chicks were placed in floor pens on previously used poultry litter (potentially providing exposure to normal chicken enteric flora) for 7 days and provided feed containing one of several antibiotics or anticoccidials. On day 7, all groups were challenged orally with an isolate of Salmonella enteritidis (10(6) colony-forming units) that was resistant to bacitracin, novobiocin, nalidixic acid, and nitrofurazone. All chicks were killed on day 13, and liver, spleen, and cecal tonsils were cultured. Dietary administration of novobiocin (0.385 g/kg) caused a significant increase (P < 0.05) in positive chick colonization rate (either liver and spleen or cecal tonsils) compared with the unmedicated controls. Similarly, chicks administered dietary nitrofurazone (0.3 g/kg) were infected with S. enteritidis at a significantly greater frequency than the unmedicated controls. A significant decrease in cecal volatile fatty acid concentration, previously shown to influence susceptibility to selected enteric pathogens, was observed in the novobiocin- and nitrofurazone-treated groups. Treatment with chlortetracycline (11.4 g/kg), monensin (0.91 g/kg), or nicarbazin (0.49 g/kg) had no effect on S. enteritidis invasion or colonization. Bacitracin (0.49 g/kg) significantly increased S. enteritidis cecal colonization rate when administered continuously throughout the study. These data support and extend previous investigations involving other salmonellae and indicate that selected antibiotics may increase the severity and frequency of S. enteritidis colonization and invasion rate in leghorn chicks.