The endogenous retroviral superantigen, minor lymphocyte stimulating antigen (Mls 1a, encoded by Mtv-7), when presented by highly purified B cells induced the development of a highly polarized population of T helper (Th)1 cells from naive peripheral CD4+ T cells in vitro. Immobilized anti-Vbeta6 antibodies similarly generated highly polarized, largely Vbeta6+, Th 1 populations in vitro. In the presence of exogenous interleukin-4, both stimuli were capable of generating Th2, rather than Th 1 populations. Mls 1a presentation by B cells in vivo led to the development of an equally polarized Th 1 population. Using monoclonal antibodies against interferon-gamma and transforming growth factor-beta, it was demonstrated that maximal Th 1 development with either stimulus in vitro was dependent on the endogenous production of these two cytokines. Thus, our results demonstrate that the retroviral encoded superantigen, Mls 1a, drives the development of Th 1 cells both in vitro and in vivo, and they suggest that B cell presentation does not, in itself, lead to the generation of Th 2 cells.