Polymicrobial peritonitis is a relatively uncommon, but potentially serious complication that develops in continuous ambulatory peritoneal dialysis (CAPD) patients. Its cause and optimal management remain controversial. The authors reviewed the frequency and natural history of polymicrobial peritonitis in 432 CAPD patients. Of 1,405 episodes of peritonitis, 80 were polymicrobial (6%). Patients with polymicrobial peritonitis were similar to all CAPD patients in age, gender, race, and underlying renal disease. Diabetes mellitus, human immunodeficiency virus (HIV) status, and clinically apparent gastrointestinal disease did not predisposes patients to polymicrobial peritonitis. Thirty days after the polymicrobial peritonitis, 64 patients remained on CAPD (80%), and at 180 days 48 patients continued CAPD. Prior exit-site infections were present in 12 patients (14%) with polymicrobial peritonitis. Only 22% of patients required catheter removal to treat the infection. We conclude that polymicrobial peritonitis accounts for 6% of the total episodes of peritonitis; diabetes, HIV infection, and underlying gastrointestinal disease are not more prevalent in patients with multiorganism infections. Most patients continue CAPD therapy at 30 and 180 days after the episode of polymicrobial peritonitis.