Anterior chamber-associated immune deviation (ACAID) expresses itself in BALB/c mice inoculated intracamerally with P815 cells in three ways: progressive growth of the tumor within the eye, transient growth of P815 cells injected subcutaneously, and prolonged acceptance of DBA/2 skin allografts. The spleen was found to play a crucial role in the development of ACAID. Splenectomized animals bearing intracameral P815 tumors reject DBA/2 skin grafts in an accelerated manner. A functioning spleen was required during the first 10 d after intracameral inoculation of P815 cells, but not thereafter. Reconstitution experiments revealed that the spleen's ability to support the induction of ACAID depends partly upon its constituent lymphoid cells, but also upon either a stromal component or a unique architectural arrangement that can only be restored with splenic fragments. The data hold promise that therapeutic protocols using appropriately timed splenectomy and specific immunization can be devised to induce hosts bearing intraocular tumors to mount an immune response sufficiently vigorous to destroy the tumor within the eye, and sufficiently precise to preserve the functional and anatomic integrity of the eye.