Efficacy studies are often performed on diseased animals while pharmacokinetic studies are conducted using healthy animals. However, drug pharmacokinetics could be altered in diseased animals as compared to the responses seen in healthy animals. Twenty four pigs (35 kg) were divided into four equal groups: a control group of normal, non-infected pigs; APP infected pigs; control, non-infected pigs given dexamethasone prior to sham infection, and APP infected pigs given dexamethasone prior to infection. Gross necropsies were conducted on all animals. Systemic levels of interleukin-6 were measured by bioassay. Pharmacokinetic calculations were performed after HPLC analysis for enrofloxacin and its metabolite, ciprofloxacin. The clearance of enrofloxacin was not altered by APP infection. Dexamethasone treatment increased the clearance of enrofloxacin in both non-infected and infected pigs. Interleukin-6 was elevated in the infected pigs. Pulmonary infection was confirmed in the infected pigs by the presence of large hemorrhagic, necrotic lesions which were up to 7 cm in diameter, consistent with clinical observations of pigs confirmed to be infected with Actinobacillus pleuropneumoniae. These results indicate that enrofloxacin clearance is not altered by this lung infection model. The concomitant use of dexamethasone with enrofloxacin may reduce drug efficacy by increasing clearance.