Transplantation of isolated islets of Langerhans is frequently followed by early loss of islet function. Because whether this is caused by insufficient vascularization or graft rejection is unknown, angiogenesis and microvascularization of islet grafts were studied in vivo by means of intravital microscopy. After transplantation of syngeneic islets in hamster dorsal skin-fold chambers, 97% (n = 66) of the islets exhibited the first signs of angiogenesis at days 2-4, characterized by sinusoidal sacculations and capillary sprouts. After 10 days, angiogenesis was completed, consisting of a microvascular network similar to those of islets in situ: arterial supply, afferent and efferent capillary loops, and venular drainage. Functional density of microvessels was 700.1 +/- 127.0 cm-1, and erythrocyte velocity was 0.58 +/- 0.35 mm/s. Intracellular insulin was demonstrated immunohistochemically. Electron-microscopic studies revealed normal fine structure of the capillary wall. The model allows in vivo analysis of microvascular phenomena occurring in host-vs.-graft reaction after allogeneic and xenogeneic islet transplantation. Furthermore, it may be used to quantitatively assess immunosuppressive regimens.