The usefulness of long-term medical treatment with somatostatin analogs has not been evaluated in insulinomas. 22 patients with hypoglycaemia related to endogenous hyperinsulinism (62±21 years, M±S.D., 2788 years) were not treated by surgery: aged patients (n=10), patients with malignant unresectable insulinomas (n=6; locally invasive, n=1; multimetastatic, n=5), multiple insulinomas (n=2), diffuse beta cell pathology (n=4). 12/22 patients underwent an Octreoscan scintigraphy. Octreotide was effective in controlling hypoglycaemia in 13/22 patients (59%): 7 aged patients, 1 patient with an invasive insulinoma, 2 with multiple insulinomas and 3 with diffuse beta cell pathology. Octreoscan scintigraphy was positive in 6/12 patients: 2 were responsive and 4 unresponsive to octreotide. Octreoscan scintigraphy was negative in the other 6/12 patients: however 3 of these patients were responsive to octreotide. Subcutaneous octreotide treatment was prolonged for more than 6 months (6 months-12 years, 5.3±4.0 years) in 10 of the 13 responders (6 elderly patients, 1 invasive insulinoma, 2 multiple insulinomas, 1 nesidioblastosis) at a dose of 502000 μg/day (495±600 μg/day). No escape to therapy was observed. However, the dose of octreotide had to be increased in 2 patients after 2 months (n=1), and after 7 years (n=1). In a patient with multiple insulinomas, subcutaneous octreotide was replaced by a long-acting somatostatin analog preparation with the same efficacy. The malignant invasive insulinoma remained asymptomatic and unchanged on CT-scan evaluation after 2 years of follow-up. Only 1 patient suffered from a symptomatic biliary lithiasis after 3 years of treatment. In conclusion, Octreoscan scintigraphy is not predictive of the efficacy of octreotide on hypoglycaemia in insulinoma patients; long-term octreotide treatment can be used to control hypoglycaemia in patients with insulinoma who cannot be cured by surgery.