A randomized prospective study was undertaken in patients on continuous ambulatory peritoneal dialysis (CAPD) to evaluate the efficacy of three different antibiotic regimens for the treatment of peritonitis. There were 39 episodes in each treatment group. Patients were treated with intraperitoneal (IP) cephalothin (250 mg/L) and tobramycin (8 mg/L) in group 1, oral ofloxacin (400 mg loading followed by 300 mg daily) in group 2, and a combination of ofloxacin (400 mg followed by 300 mg daily) and rifampicin (300 mg daily). Treatment duration was 10 days. The average culture-positive rate was 75%. The overall cure rate was 80.6% with IP antibiotics, 78.4% with oral ofloxacin, and 81.1 % with of loxacin and rifampicin. After the exclusion of tunnel infections and episodes of peritonitis due to Pseudomonas and resistant organisms, the corresponding figures were 100%, 90.6%, and 93.7%, respectively. Side effects were minimal with IP treatment and with oral ofloxacin, but severe nausea and vomiting occurred in some cases with the combination of ofloxacin and rifampicin. It was concluded that oral ofloxacin is an acceptable first-line therapy for peritonitis in CAPD patients. © 1990, National Kidney Foundation, Inc.. All rights reserved.