Infantile hemangiomas are common benign tumors of childhood. While usually self-limited, there can be significant associated morbity and mortality due to congestive heart failure, disseminated intravascular coagulation, or obstruction of vital structures, requiring aggressive medical and surgical therapy. We have treated four patients with complicated infantile hemangiomas with interferon alpha 2b therapy. The location of the hemagiomas was orbital/periorbital(2), isolated hepatic(1), and hepatic with diffuse cutaneous involvement(1). All patients initially received therapy with interferon alpha 2b (Intron A, Schering Corporation) at a dose of 3 million units/m2 as a daily subcutaneous injection. The average duration of therapy was 5.8 months with a range of 2-9 months. Duration of therapy and subsequent dose frequency were determined by clinical response. Patients in this series were either previously refractory to conventional steroid therapy or received brief courses of prednisone concommitantly, at a dose of 2 mg/kg/day for up to 4 weeks. One patient had complete resolution of an orbital hemagioma, two patients had very good partial responses with >50% involution of a periorbital and hepatic hemagiomas, and one patient with hepatic and diffuse cutaneous involvement had a poor partial response with a 25% reduction in tumor size. In the patients showing complete or very good partial response, dramatic tumor shrinkage was seen as early as 1 month after initiating therapy (range 1-6 months). In 3/4 patients, tumor shrinkage was associated with decreasing astigmatism or resolution of symptomatic heart failure. The patient showing a poor partial response had progressive heart failure and associated complications. During therapy with interferon alpha 2b, these patients experienced mildly elevated transaminases (1.5-4× baseline values), neutropenia (lowest absolute neutrophil count of 1000) and/or leukocytosis (highest WBC of 20K), which resolved upon cessation of therapy. One patient experienced a mild gross motor delay during prolonged therapy (9 months), which resolved upon completion of treatment. The patient with diffuse cutaneous and hepatic involvement experienced recurrent fevers while on interferon alpha 2b therapy, but had a course complicated by multiple infections. We conclude that interferon alpha 2b therapy is useful for the treatment of complicated infantile hemangiomas with limited reversible side effects.