One hundred and three patients undergoing biliary surgery have been entered in a randomized prospective trial for antibiotic prophylaxis. Fifty six received piperacillin (2 gr) and 47 tobramycin (100 mg). Cultures were taken from bile at operation and a clinical and microbiological assessment for infection was carried out postoperatively. Overall infection rate was significantly lower in the piperacillin group (P less than 0.05). The positive bile culture and wound infection rates were also lower in the piperacillin group, though this did not reach statistical significance. Anaerobic bacteria (three patients) and Streptococcus faecalis (one patient) were isolated in the tobramycin group. Overall postoperative infection rate was similar in patients with risk factors for infection and in those without. In conclusion, piperacillin did not significantly improve bile and wound infection rates compared to tobramycin. However piperacillin showed a more appropriate spectrum of activity. Antibiotic prophylaxis is suggested for all patients undergoing biliary surgery.