Animal models of Parkinson's disease and Alzheimer's disease have shown dramatic functional improvement after transplantation of embryonic neurons into denervated regions of the adult brain. Because of the ethical and logistic problems associated with the use of human embryonic brain tissue, cross-species transplants are an attractive alternative. An experimental model of cross-species brain transplantation was developed to evaluate cell survival in untreated and cyclosporin A (CyA)-treated animals. Cholinergic ventral neurons form embryonic mice were transplanted into the frontal lobes of 18 adult Sprague-Dawley rats using a cell suspension technique. Nine animals were treated for 13 days with CyA (10 mg/kg/day) and nine were not treated. Twelve weeks after transplantation, frozen sections through the transplant volume were obtained. Alternate sections were prepated with hematoxylin and eosin and acetylcholine esterase stains. Cell counts through a 2-cu mm volume incorporating the transplant were compared to a contralateral control volume. Eight of the nine untreated transplants were successful (mean transplant cells ± standard error of the mean: 90.7 ± 19.4/2 cu mm). All of the nine CyA-treated transplants survived, with mean transplant count 28.7 cells/2 cu mm greater than untreated transplants (mean increase 28.7: p ≤ 0.05, Wilcoxon matched-pairs signed ranks test). It is concluded that: 1) this model is useful for quantitating transplant cell survival; 2) untreated xenografts survive well; and 3) a 13-day course of CyA improved long-term graft survival.