An early differential diagnosis between bone infarction and osteomyelitis in sickle cell patients is practically impossible using routine laboratory methods. Twenty radioisotope studies in sickle cell patients during vaso-occlusive crises, were analyzed. A three stage process can be described. In the first stage a decreased uptake can be demonstrated by Tc 99m methylene diphosphonate (MDP) bone scanning. In osteomyelitis, an increased uptake area is usually seen at this early stage, corresponding to increased uptake in Ga-67 citrate scanning. At the second stage, approximately a week later, normal uptake can be seen. Two to four weeks later an area of increased uptake is recorded that corresponds to the healing process, stage three. We recommend therefore Tc 99m MDP bone scanning in the early stages if clinical signs and symptoms suggest a vaso occlusive crisis or osteomyelitis in a sickle cell patient. This study can be followed by a Ga-67 citrate scintigraphy in doubtful cases. Later studies should be used for the assessment of the healing process. Two illustrative case reports are included.