Eight patients with persistent hyperinsulinemic hypoglycemia of infancy who were treated with octreotide without pancreatectomy are described. All had severe, early-onset disease that would have required partial pancreatectomy had octreotide not been available. Along with octreotide, frequent feedings and raw cornstarch at night were required by all. Octreotide was given in three or four daily subcutaneous injections in four patients and in a continuous subcutaneous infusion with an insulin infusion pump in four. All had mild, transient gastrointestinal symptoms (vomiting, abdominal distention, steatorrhea) after the start of therapy. Asymptomatic gallstones were found in 1 patient after 1 year of treatment. No other long-term untoward effects were noted, including no detrimental effect on psychomotor development. Growth was not affected in five of six patients treated for more than 6 months. In five patients, octreotide was discontinued after 9 months to 5 1/2 years; patients were given diazoxide instead, two required percutaneous gastrostomy, and one 5 1/2-year-old child required no further treatment. The remaining three patients (aged 5 to 9 months) are still being treated with octreotide. We conclude that, with the use of octreotide, pancreatectomy can be avoided in some patients. Particularly in light of our findings of a high incidence of diabetes years after partial pancreatectomy, and clinical improvement after months to years of octreotide treatment, we believe that aggressive medical therapy, when effective, is preferable to partial pancreatectomy.