This report describes a prospective, randomized comparison of oral ciprofloxacin and intraperitoneal vancomycin/netilmicin in the treatment of 50 consecutive episodes of CAPD peritonitis in 35 patients. Successful cure of peritonitis was achieved in 76% of subjects taking oral ciprofloxacin and 72% of those given intraperitoneal antibiotics. Satisfactory concentrations of ciprofloxacin in dialysate were achieved in all patients. Failure of ciprofloxacin was due to persistence of an isolate of intermediate sensitivity (1), to persistence with acquisition of resistance (1), and to relapse/reinfection in the remaining four cases (with resistant or moderately sensitive strains in three cases). Ciprofloxacin was well tolerated in the majority of cases. A significant rise in serum creatinine was noted in almost all patients taking oral ciprofloxacin. The advantages of oral drug administration indicate that oral ciprofloxacin is the preferred first-line treatment of CAPD-associated peritonitis.