T cells on activation differentiate into different subsets (Th1 or Th2) with distinct effector functions. These T cell subsets are primarily differentiated on the basis of the cytokines that they produce, however, we have identified a novel gene family called TIM (T cell, immunoglobulin, mucin domain-containing molecules), whose members are differentially expressed on Th1 and Th2 cells. Three of the family members (Tim-1, Tim-3, and Tim-4) are conserved between mouse and man. Genomic association of the TIM family and polymorphisms in both Tim-1 and Tim-3 in different immune-mediated diseases suggest that the family may have an important role in regulating immunity, both in terms of normal immune responses and in diseases like autoimmunity and asthma.