New small barium-alginate beads produced with an original droplet generator designed in our laboratory have been utilized to encapsulate porcine pancreatic islets. The microencapsulated islets showed to be able to produce porcine C-peptide and to reverse diabetes in Streptozotocin diabetic rats and in BB/WHOR rats. Despite these encouraging results we observed a pericapsular infiltrate and a fibrotic overgrowth around the microcapsules of about 20% of the transplanted rats. Consequently, we investigated the components of the employed alginate, a Manugel DJX a low mannuronic acid concentration by Kelco which was purified and sterilized in our laboratory. Studies with HPLC showed that the alginate is composed of several fractions of different molecular weight (MW) between 1300 and 120000 Kda. Each fraction of the alginate was separated by cross-flow filters and investigated in vitro and in vivo. To characterize the porosity of the microcapsules produced with the different fractions of alginate, we have evaluated the uptake and the release of various MW fluorescein-conjugated dextrans and the release of hemoglobin from encapsulated erythocytes. These experiments showed that all the microcapsules had a cut-off of about 64000 Kda and were immunoisolating. In vivo experiments were performed in Wistar rats and in BB/WHOR rats. Empty microcapsules (n = 10000) were implanted in the peritoneal cavity of the animals. After 120 days the empty microcapsules were removed and they showed pericapsular infiltrate and capsular overgrowth in 65 + 8% of the microcapsules produced with 5000 and 30000 Kda fractions, in 78 + 5% of the microcapsules produced with 50000 and 1000000 Kda fractions, without any difference between the two groups of rats.