Bovine adrenocortical cells were transplanted into scid mice, using a small cylinder inserted beneath the kidney capsule. The tissue formed from primary bovine adrenocortical cells replaced the essential functions of the animals' own adrenal glands, which were removed during the cell transplantation procedure. Most adrenalectomized animals bearing transplanted cells survived indefinitely, whereas adrenalectomized control animals died following surgery. Formation of well-vascularized tissue at the site of transplantation was associated with stable levels of cortisol in the blood, replacing the mouse glucocorticoid (corticosterone). Ultrastructurally, the cultured cells before transplantation had characteristics of rapidly growing cells, but tissue formed in vivo showed features associated with active steroidogenesis. We investigated two potentially critical aspects of the procedure: the provision of support for angiogenesis in the transplant by the inclusion of FGF-secreting 3T3 cells with the adrenocortical cells; and the administration of synthetic steroids as a temporary replacement for steroids lost by adrenalectomy. We found that FGF was required for the rapid formation of well-vascularized tissue, whereas steroid administration avoided some early mortality but was not absolutely required. In contrast to transplants formed from clonal cells, which did not usually secrete aldosterone, transplants formed from primary bovine adrenocortical cells, even though derived from the zona fasciculata, secreted aldosterone as well as cortisol.