Background. Although af ever of unknown origin (FUO) is most often due to other causes, the few caused by pulmonary emboli, pelvic thrombophlebitis, or lower extremity venous thrombosis (DVT) present a diagnostic challenge. The purpose of this study was to evaluate the role of venous duplex imaging of the lower extremity in evaluating a large series of patients with FUO. This has not been reported previously in the English-language literature. Methods. Medical records were analyzed of patients with FUO who were referred to the vascular laboratory for venous duplex imaging of the lower extremities to rule out DVT as a cause of their fever. A FUO was defined as a temperature of greater than 38.3 degrees C on several occasions for at least 3 weeks' duration that defied 1 week of hospital evaluation. DVT was considered as a probable cause of FUO if the following criteria were met: (1) a positive venous duplex image for acute DVT, (2) subsequent fever resolution within 7 days of anticoagulation therapy, and (3) a fever that was resistant to prior treatment. Results. A total of 114 duplex examinations, gathered during a 2-year period, were analyzed. The 89 patients had a mean age of 58 years. Infections were the most common cause of FUO (57 of 89, 64%), and unknown causes constituted 19%. There were seven cases of DVT (8%), five (6%) of whom met the criteria for probable cause of FUO. The overall cost of venous duplex imaging examinations was $51,300 ($450 x 114 tests), with an average cost of $10,260 for each case of DVT detected as probable cause of FUO. Conclusions. Consistent with the literature, infections remain the most common cause of FUO; however, DVT was found to be a more common cause of FUO in our present series (6%). The cost of venous duplex imaging of the lower extremities in establishing DVT as a probable cause of FUO should be borne in mind when the work-up of these patients is planned.