Rabbits were immunized with dinitrophenylated proteins. Injections with heterologous proteins were given 11 t o 25 days after the primary injection.Spleen cell suspensions from the immunized animals were exposed to either (a) the original antigen, (b) the carrier protein of the original antigen (c) the heterologous protein used for the second injection, and (d) the heterologous protein after it was dinitrophenylated. In all the experiments a significant increase in the anti-dinitrophenyl response was obtained, whereas no such response was obtained with proteins (or their dinitrophenylated derivatives) t o which the animals were not previously exposed. The results suggest that the anti-hapten response can be significantly augmented by immunization with heterologous hapten-devoid proteins. Eur. J. Immunol. 1972.2: 290-292 Several mechanisms to explain these observations have been proposed. The possible mechanisms involve: (a) release of pharmacologically active materials [7,9], (b) expansion of helper cell population due t o cross-reaction at the level of cell receptors [8, 91, (c) graft-versus-host reaction [ 6 ] , and ( d ) multipotential cell activity. Whether one of these mechanisms, or a combination of them, can account for all the observed phenomena remains t o be seen. We wish to thank Mrs. Esther Rosenthal and Mrs, Esther Cohen for their skilful technical assistance.