Successful intrasplenic islet autotransplantation in dogs requires an islet cell mass considerably greater than what might be expected based on studies of subtotal pancreatectomy. Grafts of marginal function ultimately fail, suggesting severe limitations in the capacity of an islet graft to adapt. Accommodation was tested in established intrasplenic grafts by either chronically stressing the graft with mild carbohydrate intolerance induced by exogenous corticosteroids or chronically suppressing the graft with exogenous insulin. After these manipulations, insulin output into the portal vein in response to intravenous (i.v.) glucose was measured and compared with that of normal dogs and dogs receiving islet autografts with no further treatment with either steroids or insulin. Transplanted islets tolerated the two manipulations well in that neither exogenous steroid nor insulin led to failure of the graft as a consequence of either stress or protracted diminished demand. The major determinant of successful islet grafting is the endocrine competence of the initial graft. If that competence is provided at the outset, the graft can adapt to a considerable range of demand for insulin secretion.