Forty humane society cats with suspected bacterial upper respiratory infections (URIs) were studied in order to compare amoxycillin and pradofloxacin for treatment of rhinitis and describe common pathogens. Nasal discharges were collected prior to random placement into one of three treatment groups. Cats failing to initially respond were crossed to the alternate drug. Drug toxicity was not noted. The organisms most frequently isolated or amplified pre-treatment were feline herpesvirus-1 (75%), Mycoplasma species (62.5%), Bordetella species (47.5%), Staphylococcus species (12.5%) and Streptococcus species (10.0%). No differences in clinical scores between groups over time were noted. Overall response rates for amoxycillin at 22 mg/kg, q12 h for seven doses (10/15 cats; 67%), pradofloxacin at 5mg/kg, q24 h for seven doses (11/13 cats; 85%), and pradofloxacin at 10mg/kg, q24 h for seven doses (11/12 cats; 92%) were not statistically significant. Results suggest that pradofloxacin can be a safe, efficacious therapy for some cats with suspected bacterial URI.