BACKGROUND Hyperglycemia in the neonate may be permanent or more frequently transient. Its treatment is still debated. METHODS The files of 19 infants with hyperglycemia were retrospectively analysed. Their birth-weights were more than 900 g and their gestational ages more than 27 weeks. Plasma glucose, insulin, C-peptide, islet-cell and insulin autoantibodies were measured in each patient. RESULTS Blood glucose ranged from 1.2 to 10 g/l (mean: 5.05 +/- 1.0), between the second hour and the 60th day of life. Four infants presented with permanent neonatal diabetes mellitus: they were small for gestational age. Hyperglycemia was noted from the first day of life. C-peptide levels were less than 0.1 pmol/ml and autoantibodies were absent. Two sibs had hypothyroidism, one patient had unclassifiable chronic diarrhea plus renal disease, the fourth patient had ventricular septal defect. The 15 other patients presented with a transient hyperglycemia that appeared lately (6.1 +/- 3.4 day of life). Hyperglycemia was induced by glucose infusion in five patients, by potentially hyperglycemic drugs in five others. C-peptide levels ranged from 0.01 to 0.76 pmol/ml (mean 0.29 +/- 0.11). One patient and his mother had insulin antibodies. Another patient had congenital heart abnormalities. Hyperglycemia required insulin therapy in 17 cases (four with permanent and 13 with transient hyperglycemia). CONCLUSIONS There are no clinical or biological features permitting foresee the duration of neonatal hyperglycemia. Each patient with birth-weight below 2,500 g should be given insulin when glucosemia remains above 1.3 g/l and his weight does not increase.