Children with acute mastoiditis with periosteitis are conventionally hospitalized for parenteral antibiotics and/or surgical treatment. However, if possible, effective and safe outpatient treatment is desirable. During a 36-month period, outpatient parenteral antibiotic therapy (once daily i.m. ceftriaxone) was evaluated in 32 children with acute mastoiditis, with clinical evidence of periosteitis. Inclusion criteria included otomicroscopic evidence of acute otitis media (AOM), displacement of the pinna, retroauricular swelling, erythema and tenderness. The treatment consisted of wide myringotomy and administration of i.m. antibiotics. Daily visits, by a combined team of an otolaryngologist and pediatric infectious disease specialist, were considered essential. Fourteen children (43%) were treated initially in the hospital (and subsequently as outpatients) and 18 (57%) children were treated entirely as outpatients. Mean duration of outpatient treatment was 7 days (range: 4-10). The overall clinical cure rate was 96.8%. One child underwent simple mastoidectomy. No serious side effects were observed. Our data suggests that many children with acute mastoiditis with periosteitis can be managed successfully and safely as outpatients by a combined team of otolaryngologists and infectious disease specialists.