Background In order to avoid aminoglycosides, the International Society for Peritoneal Dialysis recommends cefazolin and ceftazidime for empirical treatment of peritonitis. Ciprofloxacin covers relevant gram-negative pathogens without the resistance associated with ceftazidime. However, ciprofloxacin pharmacokinetic data in patients on continuous cycling peritoneal dialysis (CCPD) are lacking. Objectives ( 1 ) To determine the pharmacokinetics of oral ciprofloxacin in CCPD patients, ( 2 ) to compare serum and dialysate ciprofloxacin concentrations with minimum inhibitory concentrations (MIC) of the gram-negative bacteria associated with peritonitis, and ( 3 ) to establish oral ciprofloxacin dosing guidelines for the empirical treatment of peritonitis in patients receiving CCPD. Methods Eligible CCPD patients received 2 doses of ciprofloxacin: 750 mg orally every 12 hours. Serial blood and end-of-dwell dialysate samples were collected during the first 12-hour interval; an end-of-dwell dialysate sample from the overnight dwell and a final blood sample were collected at the end of the second 12-hour interval. Ciprofloxacin concentrations were determined using a liquid chromatographic (HPLC)-fluorescence method. Pharmacokinetic calculations were completed assuming a one-compartment model. Results Eight patients completed the study. The pharmacokinetic parameters determined for ciprofloxacin were (mean ± SEM) serum half-life 10.1 ± 1.2 hours, maximum serum concentration 2.7 ± 0.5 mg/L, time to maximum serum concentration 1.6 ± 0.1 hours after the first dose, and peritoneal clearance 1.2% ± 0.1% of the mean calculated total body clearance. While all patients achieved serum area under the concentration-time curve: MIC > 125 for Escherichia coli and Klebsiella species after the first dose, only 2 patients achieved this goal for Pseudomonas aeruginosa. End-of-dwell dialysate concentrations were above the MIC for E. coli, Klebsiella spp, and P. aeruginosa after the second dose. Conclusion Ciprofloxacin 750 mg orally every 12 hours in CCPD patients may be useful for empirical gram-negative coverage of CCPD peritonitis and for treatment of documented peritonitis caused by sensitive E. coli or Klebsiella species. While ceftazidime may be required for documented pseudomonal peritonitis, the oral ciprofloxacin regimen achieved adequate serum concentrations to treat systemic gram-negative infections caused by sensitive E. coli or Klebsiella species.