All helper T cells recognise foreign protein antigens presented by class II molecules of the major histocompatibility complex (MHC) and express the cell surface molecule CD4. However, not all CD4 T cells behave as helper T cells when assayed for their ability to activate B cells to produce antigen specific antibody. In this review, after discussing the background information about CD4 T cell subsets, a series of questions will be asked: whether selective activation of distinct functional subsets of CD4 T cell accounts for the difference between humoral and cell-mediated immunity; whether the same subsets exist in all mammalian species studied to date, or whether there are major species differences; whether cells belonging to distinct functional subsets can be distinguished on the basis of a subset-specific cell surface molecule; what models of subset development can account for existing data; and whether or not the subsets defined to date are all comparable in their ability to activate B cells?