Acute lymphoblastic leukemia (ALL) is a heterogeneous disease as defined by clinical characteristics and immunologic techniques. The standard cell surface markers are sheep erythrocyte receptors for T lymphocytes and surface membrane immunoglobulin for B lymphocytes. Utilizing these markers, three subtypes of ALL designated T-ALL, B-ALL and non-B, non-T or null ALL have been defined. We have studied 70 patients with ALL utilizing these standard cell surface markers. In addition, we have further subclassified these patients by testing each cell for an ALL-associated antigen, the la-like antigen, and thymocyte antigen(s) all defined by well-characterized antisera. We can define 12 subgroups of ALL by their surface antigenic characteristics. These subgroups may have relevance to the clinical expression of disease and may define identifiable stages of normal lymphocyte development.