OBJECTIVE To investigate two related children with congenital permanent diabetes. SUBJECTS AND METHODS Two related male patients of Arab origin with congenital permanent diabetes were studied for immunological and genetic markers, insulin and glucagon secretion, thiamine levels, pancreatic ultrasounds studies and developmental characteristics. RESULTS Both patients developed normally. The immunological markers were negative, there was no ketosis at diagnosis, and both patients were negative for diabetes susceptibility alleles at the HLA locus. Insulin levels were undetectable, glucagon secretion, thiamine levels and pancreatic ultrasound studies were normal. CONCLUSIONS Congenital permanent diabetes is an extremely rare entity that differs from type I or type II diabetes. Our patients have a unique disorder with isolated beta cell defect and no additional manifestations. Autosomal recessive inheritance is suggested.