Cyclosporin A (CsA) is a potent immunosuppressant that may also affect nonlymphoid cells. Indeed, CsA exerts a growth inhibition in vitro of several human and animal, normal and neoplastic cell types. To assess a possible in vivo direct cytostatic activity of CsA, the authors evaluated the proportion of S-phase (5-bromo-2'-deoxyuridine incorporating) cells of epithelial origin (skin, tongue, esophagus) of congenitally athymic (nude) mice bearing xenografts of human skin and receiving a daily subcutaneous injection of 50 mg/kg of CsA for 3 weeks. As compared with control animals, CsA-treated mice showed a decreased labeling index (LI) of all the epithelial tissues studied, which was statistically significant in the case of epidermis (both human and murine) and the tongue. Because nude mice lack T-cell-mediated immunity, these results suggest that CsA also exerts an immunologically independent antiproliferative activity on epithelial cells in vivo and they also highlight the interest in pursuing studies on cyclosporins as cytostatic agents.