Adrenocortical cells of bovine origin and of adult and fetal human origin were transplanted subcutaneously (s.c.) in scid mice after being embedded in collagen gel. In this site the cells survived, became vascularized by invasion of host endothelial cells, and secreted steroids into the circulation. The animals' own adrenal glands were removed at the time of cell transplantation. Steroids secreted by the transplants replaced the essential functions of the animals' own adrenal glands. Adrenalectomized animals without transplanted cells died after several days, but most animals with transplanted bovine or adult human adrenocortical cells survived; fewer animals survived with transplanted fetal human adrenocortical cells. The histology of the tissues formed from transplanted cells resembled that of the normal adrenal cortex. A few proliferating cells were observed in tissue from bovine or adult human cells; there was a greater percentage of dividing cells in tissue derived from fetal cells. Subcutaneous transplantation of bovine or human primary adrenocortical cells in collagen provides a model for the study of the physiology, cell biology, and molecular biology of adrenocortical cells in a three-dimensional vascularized tissue structure in a host animal.