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A virulent strain of Mycoplasma gallisepticum (MG) was used to infect groups of 40 2-day-old poults kept in separate pens of 10 each. Of the six groups, three were treated with separate concentrations of tilmicosin, one was treated with tylosin, one remained untreated, and a final group was not infected and not treated. Mortality, clinical signs, and gross lesions were significantly less (P < 0.001) in the uninfected and infected medicated groups than in the infected unmedicated group. Also, the mean body weight gain of poults surviving to the end of the experiment was greater (P < 0.005) in the uninfected and infected medicated groups. MG was not recovered from the uninfected birds, and, among the infected poults, it was recovered from significantly fewer (P < 0.05) poults in the medicated groups. Serologic results were negative for the uninfected group, and there were fewer positive reactors for the infected medicated than the infected unmedicated group. In consideration of these results, tilmicosin should prove to be a useful addition to the antimicrobials in the treatment of MG infection in poults.