Rabbits were rendered tolerant to human albumin (HA) and were then injected with azo and oxazolonated derivatives of human albumin. These injections were continued to a time at which all animals would have lost tolerance if they had not been injected. Injection of cross-reacting antigens prolonged the duration of tolerance, as judged by the mode of elimination of lightly iodinated human albumin (HA.(131)I). Different derivatives of HA differed in their capacity to prolong tolerance. Those neonatally injected rabbits which were immunized with cross-reacting antigens and lost tolerance, responded much more promptly to HA.(131)I than animals which were not immunized. Animals immunized with cross-reacting antigen which went on to eliminate HA.(131)I triphasically, usually had responded earlier by making antibodies. These antibodies contained a fraction which was reactive with HA, and which was usually equally well adapted to determinants on HA and on the cross-reacting antigen.