The diagnosis of pedal osteomyelitis is often complicated by the presence of pre-existing bony abnormalities. In this study, the utility of radiolabeled white blood cell imaging for the detection of complicated pedal osteomyelitis was evaluated. Twenty-seven men and women were prospectively enrolled and underwent plain film radiography, three-phase bone scan, and Tc-99m hexamethylpropylamine oxine white blood cell scintigraphy of their feet. The presence or absence of osteomyelitis was confirmed in all subjects by microbiologic and histopatholigic analysis of resected bone tissue. The results indicated that white blood cell imaging was more sensitive (90%) and specific (86%) for infection than either bone scan (75% sensitive, 29% specific) or plain film radiography (55% sensitive, 57% specific). This preliminary study suggests that Tc-99m hexamethylpropylamine oxine-labeled white blood cell scintigraphy is a simple, accurate test for the detection of pedal osteomyelitis.