Lymphocytes mediate many important functions of the immune system, such as antibody production, cytotoxicity, and immediate and delayed type hypersensitivity (DTH). In 1968, two major divisions of lymphocytes were recognized: B cells (derived from bone marrow) that produce antibody, and T cells (thymus-dependent) responsible for DTH, cytotoxicity, and regulation of many B- and T-cell functions. The discovery of subset-specific cell surface antigens subsequently allowed division of T cells into two classes: mainly responsible for helper and DTH functions, T cells bearing Lyt-1 and L3T4 antigens, and T cells bearing the Lyt-2 antigen responsible for the majority of cytotoxic and suppressor functions. Evidence from studies with normal cell populations and T-cell clones has since suggested that the Lyt-1(+)L3T4(+)Lyt-2(-) helper T cell population can be divided into at least two types. In this article, Tim Mosmann and Robert Coffman review evidence for this subdivision obtained with T-cell clones grown in vitro and discuss the implications of differences in function and lymphokine synthesis between the two types of cloned helper T cell.