The efficacy of an injectable formulation of danofloxacin (180 mg/ml) in the treatment of naturally occurring bovine respiratory disease was evaluated in field studies on farms in France, Ireland and the United Kingdom. Cattle aged one week to 15 months with clinical respiratory disease were randomly allocated to treatment with 6 mg/kg danofloxacin or 10 mg/kg tilmicosin, administered by a single subcutaneous injection on day 0. A second injection of danofloxacin was administered on day 2, only if predefined clinical criteria were met. Mannheimia haemolytica, Pasteurella multocida and Haemophilus somnus were isolated from pretreatment nasopharyngeal swabs taken on all the farms. After the treatment, there was a more rapid improvement in the clinical response of the 178 animals treated with danofloxacin by day 2 (P < 0.01) than in the 90 treated with tilmicosin. For both treatments, there were similar significant (P < 0.001) reductions in the mean rectal temperature and severity of clinical signs of abnormal respiration and depression, on days 4 and 10 compared with day 0; 78.1 per cent of the animals treated with danofloxacin and 78.5 per cent of those treated with tilmicosin completed the studies. Danofloxacin 18 per cent was clinically safe and as effective as tilmicosin in the treatment of bovine respiratory disease.