The effect of route of administration and dose of enrofloxacin (Baytril(R)) on the development of fluoroquinolone resistance in Salmonella and Escherichia coli in the intestinal tract of pigs was investigated. Healthy pigs at the age of 8-10 weeks were infected with a mixture of susceptible wild-type (MICciprofloxacin = 0.03 mug/ml) and a mutant Salmonella typhimurium with reduced susceptibility to fluoroquinolones (MICciprofloxacin 0.5 mug/ml) (in the ratio 99: 1) and treated with 2.5 mg/kg bwt enrofloxacin by either intramuscular (i.m.) or oral (p.o.) administration at time points either 4 or 24 It after the infection. The treatment via the intramuscular route of administration (24 h after the infection) was carried out with elevated doses of 7.5 and 15 mg/kg bwt as well. Emergence of resistance during a 3-day treatment period and persistence up to 13 days after treatment, was monitored by counting the resistant and total number of coliforms and Salmonella in faeces of the pigs. High frequencies of fluoroquinolone resistance developed rapidly among the coliform flora independent of route of administration, dose or time of initiation of the treatment. Selection for resistance among the artificially introduced Salmonella was reduced by using the intramuscular route and by escalating the dose 3 or 6 times the recommended dose of 2.5 mg/kg bwt, which also resulted in shortening of the period, in which the pigs were shedding Salmonella. The resistance among the coliform flora persisted for at least 2 weeks. The Salmonella infection was cleared in all cases during the 2 weeks independent of frequency of resistance. The study showed that resistance is very easily selected by treatment with enrofloxacin at the recommended dose 2.5 mg/kg bwt, but also that the intensity of selection can be reduced by using intramuscular dosing (instead of oral dosing) and by escalating that i.m. dose. The results obtained with Salmonella also showed that even very small changes in the active drug concentrations might completely change the intensity of selection. (C) 2003 Elsevier Science Ltd. All rights reserved.