The efficacy of a single dose of tulathromycin, a novel triamilide antimicrobial of the macrolide class, given at 2·5 mg/kg or 5 mg/kg bodyweight, or three daily doses of ceftiofur, given at 3 mg/kg bodyweight, was evaluated in pigs with respiratory disease induced experimentally with Actinobacillus pleuropneumoniae. On day 0, 100 pigs with clinical signs of respiratory disease were randomly assigned to groups of 25 pigs, which were treated with either saline, one of the doses of tulathromycin, or ceftiofur. The pigs’ rectal temperatures and clinical scores for respiratory signs and general attitude were recorded daily until day 10. Animals withdrawn from the study for welfare reasons were recorded. On day 10, the animals remaining in the study were weighed, euthanased and examined postmortem. Three of the animals treated with saline and one of those treated with 2·5 mg/kg tulathromycin were withdrawn from the study, but none of those treated with 5 mg/kg tulathromycin or ceftiofur were withdrawn. The least squares mean bodyweight gains of the pigs treated with the antimicrobial agents were significantly (P<0·05) higher than that of the saline-treated group, and the least squares mean percentages of the total lung involvement and incidence of respiratory disease associated with A pleuropneumoniae were significantly (P<0·05) lower, but there were no significant differences between the three groups of pigs treated with the antimicrobial agents.