One hundred thirty-five children with acute osteomyelitis were identified by chart review during a 7-year period, January 1, 1980, through December 31, 1986. Bacteriologic causes were detected in 75 (55%) of the patients. Staphylococcus aureus, Haemophilus influenzae type b, and Pseudomonas aeruginosa were identified in 34 (25%), 16 (12%), and eight (6%) children, respectively. Staphylococcus aureus occurred in all age groups, H influenzae type b occurred only in children younger than 3 years and was the number one cause of disease in this group. Pseudomonas aeruginosa occurred exclusively in children older than 9 years. Children with H influenzae type b had clinical and laboratory findings that were almost indistinguishable from a matched group of children with osteomyelitis due to other known bacteria, although children with H influenzae type b tended to have more joint effusions (63% vs 27%), less lower extremity disease (22% vs 70%), and fewer positive cultures from bone or joint aspirates (41% vs 89%). Unlike most pediatric cases of osteomyelitis, the ones due to P aeruginosa did not represent the hematogenous route of infection; penetrating injury to the foot was present in every case. Children with P aeruginosa infections were older than 9 years (100%), predominantly male (88%), often afebrile (83%), and never bacteremic. These data provide guidelines for the initial work-up and management of osteomyelitis in children.