Salmonella osteomyelitis involving multiple bony sites is seen primarily in patients with sickle cell disease. Children with sickle cell disease often exhibit a syndrome consisting of bilateral, painful swellings of the hands or feet or both, with fever, leukocytosis, and bony changes that are indistinguishable from Salmonella osteomyelitis. These changes in the past have been ascribed to bony infarction. Salmonella osteomyelitis affecting both hands simultaneously and simulating the hand-foot syndrome occurred in a young Negro boy. Similar cases have been described in the literature in the past, but have received little attention. We believe that a small, but significant, percentage of cases of the hand-foot syndrome are caused by osteomyelitis.