AbstractSeveral approaches have been used in our attempts to increase the “natural” ability of normal T splenocytes (Tn) from BALB/c or BC8 mice (both Igha) to induce, in F1hybrids, a suppression of Igh‐lb expression (IgG2aof b haplotype). These heterozygous F1were produced by mating these Ighamice and their Ighb‐congenic partners (CB20 and C57BL/6, respectively). The most powerful approaches were to sensitize the Ighamice by either autologous splenocytes coated with Igh‐lb or B splenocytes from Ighb‐congenic mice. In F1having paternally inherited the b haplotype the sensitized T splenocytes (Tn) prepared from such mice are able to induce, like Tnwhen injected at birth, a chronic suppression of Igh‐lb expression. However, the suppression was established with a much higher efficiency: already at 6 weeks of age in 100% of the F1treated with 1 × 107Tsvs.a final rate of 70% progressively reached only at 42 weeks of age in the F1treated with 4 × 107Ts. In F1having maternally inherited Ighbthe differences were even more pronounced than with 4 × 107Tni.e.the suppression induction was almost totally ineffective, whereas with 2 × 107−4 × 107Tsa rate of 100% treated F1subjected to suppression was reached at 19 weeks of age. As the productions of IgM, IgD and IgA of the b haplotype were not affected by the suppression, the Tsare believed to act on the Igh‐lb′ cells. Attempts were also made to induce allotypic suppression of other b allotypes by the use, as sensitizing cells, of myeloma cells carrying Igh‐6b (IgM of b haplotype). We failed in revealing any sign of a T cell reactivity against Igh‐6b similar to the reactivity against Igh‐lb. The use of Igh‐6b+myeloma cells grown in an Igh′ or in an Ighabackground allowed us to assume that the cells responsible for the sensitization are, in the IghbB lymphocyte population, either the Igh‐lb+lymphocytes or the lymphocytes having passi