The controlled release of insulin from ethylene-vinyl acetate copolymer matrices wasdemonstrated for over 100 days in vivo. The matrices were designed to release sodium insulin at near-constant rates. These 0.06-cm3 implants were coated completely with an impermeable layer of polymer. An aperture was drilled in the center of one face of the matrix, restricting release through this opening. These devices were implanted into 13 streptozocin-induced diabetic rats. Plasma glucose concentrations fell from 386 ± 18 to 119 ± 35 mg/dl (mean ± SEM), and urinary glucose was eliminated. Thee parameters were controlled for up to 105 days by a single implant. Glycosylated hemoglobin concentrations measured 90 days after implantation were 3.86 ± 0.11% for the polymer-treated rats, 3.10 ± 0.18% for the normal controls, and 5.42 ± 0.33% for the diabetic controls. The average weight gain of the treated rats was similar to that of the controls, whereas the diabetic controls failed to thrive. In addition, all of the diabetic controls developed cataracts 1 mo after diabetes induction, whereas none of the treated rats developed cataracts.