1. A crude semi-soluble extract of A-strain lymphoid tissues will sensitize C3H mice to A-strain skin grafts when given i.p., but not when given i.v. Intravenous injection of semi-soluble antigen sometimes prolongs the life of homografts. 2. Both its physical form and its route of entry determine whether or not a given antigenic preparation from A-strain mice will sensitize C3H mice. Sensitization is least effective when the i.v. route is used, but antigen in a particulate form will sensitize even when given i.v. and antigen in a soluble form will not sensitize even when given i.p. 3. In the combination C3H → CBA, chosen to typify a weak histocompatibility system, both soluble and particulate antigenic extracts prolong the life of homografts in adult mice when administered in adequate doses through i.v., i.p., or subdermal routes. 4. Antigens administered in such a form or in such a way that they do not excite transplantation immunity may yet excite transplantation tolerance. 5. So administered, antigen acts in synergism with X-irradiation, a-methopterin, or hyperimmune isoantibody (but not with trypan blue) to prolong the life of homografts more effectively than do any of these agents acting alone. 6. The states of anergy or hypoactivity produced by the concerted action of antigen and immunological depressants must be classified as forms of tolerance or paralysis, not as forms of ‘enhancement’.