Sickling of erythrocytes in patients with S-hemoglobin causes marrow and bone infarction. The former can be demonstrated as a lack of 99mTc-sulfur colloid uptake on marrow imaging examination. These defects may resolve or persist long after the acute episode. If the bone is involved in the acute episode, imaging within the first few days of onset of symptoms can show lack of 99mTc-labeled phosphate uptake, usually in a smaller area than that shown by marrow scanning. Follow-up bone imaging shows increased activity, particularly along the circumference of the bone where periosteal reaction can be demonstrated radiographically. Magnification by use of the pinhole collimator provides better definition of the uptake defect and the distribution of the increased reactive uptake. Timing of examination is important. If marrow imaging is performed in an asymptomatic period, the repeat examination during a painful crisis permits differentiation of old and acute marrow infarction. If 99mTc-phosphate imaging is performed after about 2 days of symptoms, acute infarction can be differentiated from osteomyelitis, which it may mimic clinically. Although osteomyelitis may cause no increased activity in the first 48 hr after onset of symptoms, it is characterized by intense focal activity thereafter (see article by Handmaker in this issue). To assist in differentiating bone infection in a site of marrow infarction demonstrated by marrow imaging, serial bone imaging with magnification may be useful. The uptake defect, followed in several days to 2 weeks, by circumferential increased activity, is a different pattern than the homogeneously intense activity of osteomyelitis, but the peripheral distribution may not be apparent on routine imaging. It is hoped that the utilization of these techniques can decrease the emotional and economic costs of prolonged hospitalization for suspected infection and can also expand our knowledge of the complex pathophysiologic changes of sickle cell bone disease.