H-2d mice treated before skin grafting with either soluble alloantigen prepared from H-2b cells or with serum obtained from similarly sensitized mice showed a significantly prolonged survival of H-2b skin allografts. This in vivo enhancement was paralleled by a depression of cell-mediated cytotoxicity to [51Cr]H-2b target cells in vitro. Such in vitro and in vivo effects were abrogated when mice were repeatedly injected with soluble alloantigen before and after skin grafting, demonstrating that enhancing antibody present could be neutralized by this mode of antigen administration. The data suggest that serum factors present in mice pretreated with soluble alloantigen lead to specific blocking at the induction phase of the cell-mediated immune response and result in skin graft enhancement.