The role of prophylactic antibiotic lavage in elective biliary tract operations is controversial. To investigate this question, a prospective, randomized study was undertaken between 1979 and 1983. All patients more than 18 years of age who underwent elective biliary operations were included. Eighty-eight patients were enrolled in the study and were stratified into the following antibiotic groups: (1) cefamandole nafate 2 gm administered intravenously preoperatively and 6 hours postoperatively in four doses; (2) cefamandole nafate 0.4% solution: 250 ml to irrigate the abdominal wound on opening, 500 ml to irrigate the peritoneal cavity, and 250 ml to irrigate the wound on closing; and (3) systemic plus topical administrations as in Nos. 1 and 2. Age, sex, type of operation, and underlying diseases were comparable in all groups. The patients were then evaluated for postoperative infections. In the intravenous cefamandole group there was only one patient who developed a urinary tract infection after operation. In the topical cefamandole group there were four postoperative infections: wound-one, urinary tract--two, and cholangitis--one. In the intravenous plus topical cefamandole group there were four postoperative infections: wound--one, urinary tract--two, and pneumonia--one. No deaths occurred in any group. Blood, subcutaneous, and peritoneal drug levels were sampled 1 hour after opening and before closing. Therapeutic serum levels of cefamandole are 1 to 16 micrograms/ml and adequate serum levels were achieved in all groups. However, higher levels were obtained in the subcutaneous tissue and peritoneum when topical cefamandole was used. We conclude: (1) Topical cefamandole lavage alone is adequate prophylaxis in elective biliary operations and achieves comparable results as perioperative systemic administration; (2) topical cefamandole resulted in higher subcutaneous tissue and peritoneal levels than intravenous cefamandole and also achieved therapeutic serum levels; and (3) there is no advantage to the use of systemic plus topical antibiotics in elective biliary operations.