Six unstable C-peptide negative type I diabetic patients who had been previously treated with continuous subcutaneous insulin infusion (CSII) for at least one year without achieving satisfactory metabolic control, were admitted to this study and switched to continuous intraperitoneal insulin infusion (CIPII). The results obtained with the two treatments have been compared from the metabolic and clinical points of view. CIPII produced a decrease in HbA1c (p less than 0.05), in MAGE value (p less than 0.005), in the percentage of blood glucose determinations above 14 mmol/l (p less than 0.05) and below 3.9 mmol/l (p less than 0.05); an increase in serum cholesterol, and a decrease in HDL-cholesterol (p less than 0.05) due to a reduction of the HDL2 fraction (p less than 0.01). A mean body weight reduction of 3 kg was observed during CIPII (p less than 0.01), not related to dietary changes or to a reduction of the daily insulin dose. Twenty-four hour metabolic profiles during CIPII showed lower mean plasma glucose (p less than 0.001), serum free insulin (p less than 0.001), blood beta-OH-butyrate (p less than 0.001), and higher serum glycerol (p less than 0.001) as compared to CSII. It is concluded that CIPII may be of clinical value in the out-patient management of unstable type I diabetic patients, and that metabolic modifications induced by CIPII are not limited to changes in glucose utilization and production, but include changes in triglyceride, cholesterol and lipid metabolism which may have clinical relevance.