Thirty-one cats showing clinical signs of upper respiratory tract disease with a presumed bacterial component based on clinical signs were administered either amoxycillin or azithromycin to determine which drug protocol was optimal for empirical use. A clinical score was determined and nasal and pharyngeal swabs were collected for bacterial culture, virus isolation and polymerase chain reaction prior to the start of therapy. Cats failing to respond to the initial antibiotic were then administered the other drug. There were no differences in clinical scores between the two groups at the start of therapy. Eleven of 31 cats improved after administration of the first antibiotic, 16 cats were switched to the alternate antibiotic, and four cats were removed from the study for additional supportive treatments. Eight of 27 cats failed to respond to either antibiotic. The chi2 test for outcomes revealed no differences in response to therapy for either antimicrobial.