The use of open-loop devices in unstable diabetes has led to controversial results. This is likely to be due to the fact that heterogeneous clinical conditions have been classified as unstable or brittle diabetes. In a cross-over protocol we have studied seven unstable diabetics characterized by elevated glycosylated hemoglobin (HbAUI), increased number of hospital admissions, frequent urinary finding of ketone bodies, despite a multi-injection regimen of insulin therapy. All the patients showed a C-peptide secretion in the low range. The diabetic subjects were randomly allocated, either to continuous subcutaneous treatment, or to traditional intensive insulin therapy (three doses of regular plus lente at bedtime), and crossed over to the second treatment after one month. Continuous subcutaneous treatment reduced fasting blood sugar from 283 to 108 mg/dl, p < 0.02, glycosuria from 15 to 7.5 g/24 h, p < 0.05 and HbA| from 10.8 to 8.8%, (p < 0.05). The split insulin therapy reduced glycosuria, but did not affect significantly blood glucose and HbAI. After continuous subcutaneous treatment, patients showed a decrease of insulin requirement (p < 0.05), a lower level of mean daily plasma free insulin (p < 0.05), and a reduced degree of free insulin excursions over the mean daily value (p < 0.01). We conclude that in unstable diabetes continuous subcutaneous insulin therapy is effective, albeit not capable of inducing normalization of metabolic control; the amelioration of metabolic condition is accompanied by a decrease of daily insulin need, of the mean daily plasma free insulin levels and of the amplitude of circulating insulin oscillations. Yet being unproved a clear cut superiority of this therapeutic approach over the traditional intensive split insulin regimen, this alternative should be also considered.