The efficacy of chlortetracycline (CTC) in-feed medication to treat pigs with clinical respiratory disease was investigated in a farrow-to-finish pig herd infected with Mycoplasma hyopneumoniae, and with clinical respiratory disease in growing pigs. In total, 533 pigs were included. The animals were vaccinated against M hyopneumoniae and porcine circovirus type 2 at weaning. At onset of clinical respiratory disease, they were randomly allocated to one of the following treatment groups: chlortetracycline 1 (CTC1) (two consecutive weeks, 500 ppm), chlortetracycline 2 (CTC2) (two non-consecutive weeks, with a non-medicated week interval in between, 500 ppm) or tylosin (T) (three consecutive weeks, 100 ppm). Performance (daily weight gain, feed conversion ratio), pneumonia lesions at slaughter and clinical parameters (respiratory disease score) were assessed. Only numeric differences in favour of the CTC2 group were obtained for the performance and the clinical parameters. The prevalence of pneumonia lesions was 20.5, 13.1 and 23.0 per cent (P<0.05) for the CTC1, CTC2 and T groups, respectively. The study demonstrated that CTC, when administered at onset of clinical respiratory disease via the feed at a dose of 500 ppm during two alternative weeks, was able to decrease the prevalence of pneumonia lesions, and numerically reduce performance losses and clinical signs.