Rats rendered tolerant to ultracentrifuged sheep γ-globulin (ShIg) make a poor anti-trinitrophenyl- (TNP) specific antibody response upon challenge with TNP-ShIg in adjuvant. This system has been utilized to investigate the specificity of carrier recognition in tolerance. Induction of tolerance to heterologous globulins (goat, bovine, horse, pig, and rabbit) produced varying degrees of cross-tolerance upon challenge with TNP-ShIg. The cross-reactivity was similar to that seen when ShIg-sensitized cells (immune) were stimulated in vitro to incorporate tritiated thymidine by heterologous globulins. However, rat antibody to ShIg showed more restricted cross-reactivity than either carrier cross-tolerance in vivo or cross-stimulation in vitro. This suggests that carrier recognition in both tolerance and cell-mediated immunity is similar and provides further evidence for broader reactivity in cell-mediated (T cell) than in humoral (B cell) immunity.