Results of cultured islet transplantation in the management of insulin-dependent diabetes are still unsatisfactory. The main problem preventing success is the swift and resolute host immune rejection. To obviate this we designed and experimented a model of bioartificial pancreas, made of polymeric hollow fibers, put into the blood circulation as an artero-venous bypass to immunoisolate endocrine tissue from leucocytes and immunoglobulins. We tested four different membrane bioreactors (BR1-4). BR1 and 2 had seven hollow fibers, the others more than 6,000 smaller fibers. In BR4 a connecting tube with a high-permeability membrane was inserted between the islet compartment and the bioreactor outlet to improve the ultrafiltration flow. In vitro, the islets inside the bioreactor perfused with glucose solutions (300 mg%) showed a rapid, high insulin secretory response, related to the glucose stimulation. The use of the outside connection allowed a twofold increase of insulin production.