It was found that freshly isolated BALB/c CD4+ T cells produced high levels of IL-4 and IL-10 in response to immobilized anti-CD3 mAb, while C57BL/6 CD4+ T cells produced low amounts of IL-4 and IL-10. The high IL-4-producing ability of BALB/c mice was demonstrated to be genetically dominant and it was controlled by non-MHC gene (or genes). The cells responsible for IL-4 production in BALB/c mice were defined as TCRVbeta8.2+ CD4+ CD62L- CD45RB- memory-type T cells, which were distinct from NK1.1+ CD4+ NKT cells. Although these memory-type T cells were also detected in C57BL/6 mouse spleen at the same frequency, they showed a functionally different property from BALB/c CD4+ CD62L- CD45RB- T cells in terms of IL-4 production. The fact that germfree BALB/c mouse spleen cells also produced high levels of IL-4 suggested that the IL-4 producer in BALB/c mice might be developed under the influence of unknown factors other than environmental Ags. The CD4+ CD62L- CD45RB- T cells obtained from BALB/c mice accelerated the development of IL-4-producing memory-type CD4+ T cells from CD4+ CD62L+ CD45RB+ naive T cells prepared from OVA-specific TCR-transgenic mice. Therefore, IL-4-producing CD4+ CD62L- CD45RB- T cells might play an important role in the preferential induction of Th2-dominant immunity in BALB/c mouse strain.