The instability of insulin in the reservoirs of implantable insulin delivery devices has been a major obstacle in implementing this form of therapy. To overcome the problem of precipitation, a glycerol-insulin preparation has been used in large-scale long-term clinical trials. The aim of this study was to evaluate the stability of the glycerol-insulin solution and its effects on circulating insulin antibodies in eight type I diabetic patients who were implanted with an Infusaid pump (Infusaid Corporation, Norwood, MA) and followed for 1 year or more. Total insulin requirement did not change throughout the observation period. Plasma free insulin was higher during treatment with glycerol-insulin than with the standard insulin treatment (P less than .02). Insulin antibodies increased in all patients (P less than .05). High-performance liquid HPLC analysis of insulin samples from the pump reservoirs showed the generation of insulin modification products at a daily rate of 1.84%, reaching 40% to 50% of the total reservoir content 3 weeks after refilling; among these products, high molecular weight species accounted for about 15%. It is concluded that glycerol-insulin is not an adequate insulin preparation for use in implanted devices. Insulin deteriorated in the pump reservoirs, and insulin antibody concentration increased in the treated patients. It is believed that this antibody production is favored by circulating insulin fragments and polymers of insulin generated inside the pump reservoirs.