The influence of enrofloxacin administration (5 mg/kg) for five consecutive days on the occurrence of Pasteurella multocida in the upper respiratory tract of two healthy calves was monitored over a 10-day period. From nasal swabs of two additional healthy control calves, which received a placebo saline administration, P. multocida was isolated throughout the study period. In the enrofloxacin treated calves, P. multocida was not demonstrated in the nasopharynx from 48 h after the first injection until two days after the last administration, when P. multocida reappeared and proved to be clonal in nature to the original isolates. During the experiment, no change in minimal inhibitory concentration for enrofloxacin of the P. multocida isolates was detected (MIC < or = 0.015 microg/mL). Enrofloxacin concentrations were determined in the plasma by a high-performance liquid chromatography method with fluorescence detection. The PK/PD indices AUC/MIC and Cmax/MIC ratio were calculated and found to be 1157.7 and 129.8, respectively. Remarkably, the respiratory pathogen Arcanobacterium pyogenes became the predominant recovered organism in the nasopharynx of one animal following enrofloxacin therapy throughout the remaining of the experiment.