To elucidate the adrenergic responsiveness of transplanted pancreatic islets, normal BALB/c mice received 150 syngeneic islets under the left kidney capsule. After 12-40 weeks, the grafts were removed and compared with untransplanted islets by an in vitro perifusion technique. Noradrenaline (NA), 3 mumol/l, completely inhibited glucose-stimulated insulin release from untransplanted islets but not from grafts, whether or not the beta adrenergic blocker, L-propranolol, was present. UK-14,304, an alpha 2-specific adrenergic agonist, inhibited glucose-induced insulin secretion from untransplanted islets by 80-92% at 0.1 or 1 mumol/l, and by 35-56% at 5-10 nmol/l. Insulin secretion from islet grafts was also markedly inhibited by 0.1 or 1 mumol/l, but not by 5 or 10 nmol/l, UK-14,304. It is suggested that the diminished adrenergic inhibition of insulin release from islet grafts reflects an altered function of the alpha 2 adrenoceptors on the beta-cells.