To date, only ofloxacin has been approved by the US Food and Drug Administration for treatment of ears with a nonintact tympanic membrane. The purpose of this study was to determine the safety and efficacy of topical ciprofloxacin hydrochloride in the treatment of experimental chronic suppurative otitis media caused by Pseudomonas aeruginosa infection in cynomolgus monkeys. Forty adult cynomolgus monkeys were divided into 4 equal groups, and their ears were challenged with P aeruginosa, drained for 3 weeks, then treated twice daily for 4 weeks with 1 of 4 randomly assigned agents: 1) ciprofloxacin, 2) saline, 3) Cortisporin, or 4) vehicle. The animals were followed up with auditory brain stem response testing, culture, otoscopy, and histopathology. Both ciprofloxacin and Cortisporin treatment resulted in a significantly more rapid rate of clearance of P aeruginosa as compared to treatment with saline (100% versus 20%). Eradication was not associated with resolution of otorrhea after a 4-week period of treatment. There were no significant changes in auditory brain stem response wave latencies for any of the treatment groups. Histopathologic data revealed that there was no statistically significant difference in the amount of outer hair cell loss for the ciprofloxacin group as compared to the control ear and other treatment groups. We conclude, therefore, that topical ciprofloxacin is not ototoxic and is effective in sterilizing the otorrhea, but does not promote resolution of the drainage, in this animal model.