The effects of in vitro dendritic cell (DC) depletion on the survival of epidermal sheet allografts were studied in a murine model. Newborn (1–3 days old) mouse skin was used. Langerhans cell (LC) and Thy-1+ dendritic epidermal cell (Thy-1+ DEC) depletion was achieved using: (1) a prolonged culture period (7 days), or (2) the anti-IA and anti-Thy-1.2 mAbs followed by complement treatment. DC (LC and Thy-1+ DEC) depletion was assessed on sheets and cultured cell suspensions by an indirect immunofluorescence procedure. They showed that, after 7 days of culture or after the antibody-complement treatment, epidermal cultures were depleted of LC and Thy-1+ DEC. Cultured sheets were grafted onto the muscle of H-2-incompatible recipients. The control experiments were: (1) full epidermis and DC undepleted sheet allografts, and (2) DC depleted and undepleted sheet isografts. The full epidermis was totally rejected after 9 days. However, no rejection sign was ever seen in any of the isografts. The in vitro produced and allografted epithelia did not show any necrotic sign until the 11th day postgrafting. However, on days 12–13, the DC depleted allograft's color changed from pink to brown. On days 14–16, degradation of the allografts resulted in a complete denudation of the underlying muscle. Immunohistological analysis of the allografts revealed the presence of a monocyte and lymphocyte infiltration starting from the 11th day postgrafting, with the presence of polymorphonuclear leukocytes on day 14. These results suggest that LC and Thy-1+ DEC depletions were not sufficient to prevent allograft rejection.