The natural history of brittle diabetes is unknown. We have followed up 13 patients with disabling brittle diabetes unresponsive to continuous subcutaneous insulin infusion (CSII) for 3-6 yr. All were young, C-peptide deficient females. One patient has died (of hypoglycaemia). In the others, disruption of life has generally lessened, but only one patient is currently considered metabolically stable. Insulin treatment regimens have included long-term intravenous insulin infusions and intraperitoneal insulin, but all but four have now reverted to subcutaneous injections. Eleven patients intermittently required greater than 200 U/day of insulin and two have needed greater than 1,000 U/day. Insulin dosages have fallen significantly during follow-up (from 6.8 +/- 3.1 to 1.4 +/- 0.3 U/kg/day). Diabetic complications, initially present in only 2 cases (1 cataract, 1 proliferative retinopathy), have now developed in 5 others (2 background retinopathy, 1 proliferative retinopathy, 1 mixed peripheral neuropathy and 1 intermittent proteinuria). Psychosocial disturbance and non-compliance were common. We conclude that brittleness generally seems to improve, which probably explains the scarcity of older brittle patients. However, these patients are at considerable risk from diabetes, its complications and its treatment.