We have compared the immune responses of mice immunized either with α‐galactosylceramide (α‐GalCer), capable of eliciting a CD1‐metiated stimulation of Vα14⁺ NK T cells, or with lipoarabinomannan (LAM), a glycophospholipid derived from mycobacteria which is known to be presented by CD1b in humans. Within 24 h, α‐GalCer induces a burst of IFN‐γ secretion in vivo, and recall with antigen in vitro leads to the synthesis of IL‐4 and IL‐10 in addition to IFN‐γ. Associated with this in vivo cytokine release is a polyclonal activation of splenic B and T cells. CD1‐reactive NK T lymphocytes mediate these events, because none of them are observed in α‐GalCer‐immunized CD1^{− / −} mice. LAM immunization fails to promote similar early responses in vivo. Repeated exposure of mice to α‐GalCer induces splenic T cells to secrete IL‐4 and IL‐10 but dramatically reduced levels of IFN‐γ. Such a biasin the cytokine balance triggered by NK T cells stimulated with multiple doses of α‐GalCer suggests that this compound might be useful in the induction of Th2 immune responses and the prevention of chronic inflammatory conditions mediated by Th1 cytokines.