T here is evidence that intraislet cellular communication and hormone delivery within the islets of Langerhans is controlled via capillary perfusion directed from the B cell core to the A/D cell mantle (intraislet portal system). To determine whether vascularization of freely transplanted islets repeats this "core-to-mantle" capillary perfusion, hamster islets were isolated by collagenase digestion and transplanted into a skinfold chamber of syngeneic animals (n = 12). 14 d after transplantation, the microvasculature of the islet grafts was analyzed by in vivo fluorescence microscopy. The capillary glomerulum-like network of the islet grafts (n = 109) was found supplied by individual arterioles, which regularly pierced the islet and broke into capillaries within the graft (96/109 [88.1%]), resulting in capillary flow directed from the core to the islet's periphery. Only in 13 of 109 islets (11.9%) arterioles broke into capillaries at the outside margin of the islet and capillary flow was directed simultaneously to vessels located within the core, as well as the periphery of the graft. The islet's capillary network was drained by individual venules and intercapillary anastomoses between the newly formed islet capillaries and the preexisting capillaries of the host muscle tissue. Immunohistochemical staining revealed B cells located within the core, and A and D cells scattered in the periphery of the islets, indicating reestablishment of sequential B-->A/D cellular perfusion of the grafts. Thus, freely transplanted islets develop an intra-islet portal system, similarly to that of pancreatic islets in situ.