A 49-year-old black man with hypertension-induced chronic renal failure requiring hemodialysis and a history of arteriovenous access graft infection was admitted with Staphylococcus aureus sepsis, dyspnea, and peri-incisional erythema over his arteriovenous graft fistula. Results of a transthoracic echo demonstrated aortic sclerosis and concentric left ventricular hypertrophy. Results of a whole-body In-111 white cell (WBC) scan were negative over the arteriovenous graft site; however, an intense abnormal focus of labeled WBCs was evident to the left of the sternum. A subsequent transesophageal echocardiogram showed a mixed cystic-solid calcified mass adjacent the left aortic cusp. Surgery confirmed a perivalvular abscess. As a whole-body imaging modality, the In-111 WBC scintigram indicated the true location of the infectious process responsible for the patient's sepsis. The combination of echocardiography and radiolabeled WBC imaging increases sensitivity for detection of endocarditis/perivalvular abscess. Radiolabeled WBC imaging is more efficacious for monitoring therapy because the echocardiogram often does not change with treatment of endocarditis/perivalvular abscess.