Thrombotic and infectious complications are frequent causes of hemodialysis vascular access failure and contribute considerably to the cost of care for chronic hemodialysis patients. Although there is clear indication for removal of patent grafts in unresolved bacteremia, there are no guidelines for the management of clotted nonfunctioning grafts. To evaluate for the existence and clinical relevance of silent infection in clotted nonfunctioning hemodialysis grafts, a study was conducted with a series of 20 hemodialysis patients who presented with fever (15 patients), or fever and clinical signs of sepsis (five patients), in whom the source of infection was not immediately localized to any organ system. Comparison was made with 21 asymptomatic patients with clotted grafts who served as control subjects. All patients and control subjects came from a pool of 115 chronic hemodialysis patients in an outpatient hemodialysis unit in the Houston metropolitan area, who were on hemodialysis for a period of time ranging from 3 to 15 yr. Indium scans were performed, followed by removal of the clotted grafts in all patients and control subjects. Bacterial cultures of the recovered surgical material and blood were done concomitantly in all study participants. Indium scans showed positive uptake in or around the clotted grafts in all of the patients and in 15 of the control subjects. Purulent material was found in the grafts in all patients and in 13 of 15 indium scan-positive control subjects. When positive, blood culture pathogens were identical to those cultured from the graft material in all instances. The predominant pathogens were Staphylococcus aureus, followed by Staphylococcus epidermidis. There was no evidence of graft infection in the control subjects if indium scan was negative. Chart review dating back to the start of dialysis revealed five past infectious episodes in the patient group, compared with four in the control group. These findings suggest that clotted nonfunctioning grafts are frequent harbingers of infection. They should be suspected as the source of infection in every hemodialysis patient that presents with fever, even in the absence of clinical signs of graft site infection.