Isolated porcine islets represent a potential source for discordant islet xenografts in diabetic patients. The authors therefore investigated insulin secretion from isolated porcine islets both in vitro and in vivo. For in vitro studies, islets were maintained in culture or placed in biohybrid perfusion devices consisting of a plastic housing containing a selectively permeable acrylic copolymer tubular membrane. Culture medium was circulated through the devices in a closed loop system. After 3 months the cultured islets secreted insulin at levels of 354 +/- 49 microU/equivalent islet number (EIN)/day (mean +/- standard error of the mean [SEM]; n = 10). They responded to glucose stimulation (5 to 16 mmol/L steps) with significant increases in insulin secretion. The biohybrid devices seeded with islets produced 23 +/- 2 (mean +/- SEM; n = 8) units insulin per day over periods of 83 +/- 8 days. For in vivo studies, islets were sealed within membrane chambers and implanted in the peritoneal cavity of streptozotocin induced diabetic Lewis rats. Chambers with a total of 2 x 10(4) islets per rat normalized the plasma glucose values of 10 rats, with the concentrations decreasing from 487 +/- 18 to 97 +/- 10 mg/dl during the first month. All grafts maintained normoglycemia for longer then 3 months. Histologic studies of long-term chamber implants in rats (1-20 months of age) showed viable islets, with varying degrees of beta cell granulation. These studies suggest the long-term functioning of porcine islets both in vitro and in vivo as discordant xenografts.