The biliary tract excretion of cefamandole, cefazolin, and cephalothin was measured in eight patients with T-tubes inserted into their common ducts after ductal exploration for biliary tract stones. Each patient received 1.0 g intravenously of each cephalosporin on 3 separate days; T-tube bile and serum were collected at selected time intervals thereafter. In seven patients, bile and urine were collected for 6 h after the administration of each drug. Mean peak levels of cefamandole, cefazolin, and cephalothin in bile were 352, 46, and 12 mug/ml, respectively. The respective mean peak serum levels were 55.0, 92.8, and 32.4 mug/ml. Despite the fact that peak serum levels of cefazolin were 1.5 times those of cefamandole, levels in bile of cefamandole were about 8 times those of cefazolin. Over a 6-h period, almost three times as much cefamandole was excreted into bile as was cefazolin. Therefore, in those patients with biliary tract sepsis, in whom a cephalosporin is indicated for therapy, cefamandole appears to be the drug of choice.