The present study investigated the histologic maturation, proliferative capacity, and steroid production of fetal adrenal transplants (Tx) in adrenalectomized rats. A pair of fetal adrenal glands (18-20 days of gestation) was transplanted into the omentum of syngeneic Lewis rats (n = 45). Four weeks later, in 5 animals the grafts were excised for morphologic evaluation. Proliferation was investigated by immunohistochemical staining for KI-67 protein and quantified by the proliferation index (PI = positive cells/100 counts). All other hosts (Tx; n = 40) underwent bilateral adrenalectomy (AE) to induce Addisonian crisis. Postoperatively, survival and concentrations of potassium, sodium, aldosterone, and corticosterone were recorded for 6 months. These data were compared to controls (C=only AE; n = 30) and a sham group (S; n = 10). At the end of the study period all surviving hosts were killed for histologic examination of grafts. At 4 weeks post-Tx the adrenal grafts demonstrated a distinct zona glomerulosa and frequent proliferation with a PI of 0.084, comparable to normal control (0.092). Following AE survival was significantly prolonged in Tx (86% vs 12% of C, P < 0.05). Control animals developed severe hyponatremia and hyperkalemia, whereas in Tx only transient signs of Addisonian crisis were recorded. Levels of aldosterone dropped within 7 days in the Tx and C groups, but returned to normal for Tx within 8 weeks. Corticosterone levels of Tx animals fell to 25% within week, but steadily increased to 70% by the end of the study. At 6 months, grafts revealed a mature adrenocortical structure with little proliferative activity, which was comparable to controls. In a syngeneic rat model fetal adrenal transplants thus mature and proliferate to provide sufficient steroid production for adrenalectomized hosts.