Position-effect can be engineered in lymphocytes when positive cis-acting sequences are deleted from a uniformly expressed gene, resulting in an infrequent or variegated pattern of expression (Festenstein et al., 1996). The initial cell divisions following polarized T cell differentiation appear variegated. All cells may be signaled to become either Th1 or Th2 cells, but only small numbers initially adopt effector fates (Bucy et al., 1995; Bird et al., 1998). A model predicting that Th1 and Th2 cells arise from a common precursor cell expressing multiple cytokines (Kamogawa et al., 1993) is seemingly at odds with a model suggesting variegated initial appear-