Most prospective studies recommend antibiotic prophylaxis whilst a thoracostomy tube is in place or even longer. We conducted a randomised study of 188 patients with penetrating chest injuries requiring a chest drain. Of these patients, 95 received a single dose of ampicillin before insertion of the chest tube, the remaining 93 patients received additional antibiotic prophylaxis for as long as the drain was in place. The incidence of intrathoracic sepsis (pneumonia or empyema) was 3.1% and 3.2%, respectively. It is concluded that single-dose prophylaxis in penetrating chest trauma is as effective as prolonged prophylaxis. The importance of chest physiotherapy immediately after the drain insertion and of early removal of the drain is stressed. The role of various possible risk factors in the development of sepsis is discussed.