N ormal human peripheral blood T cells can be characterized as belonging to either the TH+2 or TH-2 T-cell subset. Approximately 20% of T cells are TH+2, whereas 80% are TH-2 utilizing specific heteroantisera. To determine shether human T-cell acute lymphoblastic leukemia (T-ALL) cells belong to one or another T-cell subset, cell surface phenotyping was performed on tumor populations from 25 patients with T-ALL. Tmuor cells from these 25 individuals were either TH+1 or TH-2, but not both. 5 of 25 patients had TH+2 T-ALL cells. These TH+2 tumor populations were found exclusively in children and often without an accompanying thymic mass. TH-2 T-ALL, in contrast, occurred in both children and adults and was almost always associated with thymic enlargement. Although children with TH+2 T-ALL had as high or higher peripheral blast counts on presentation than their TH-2 T-ALL counterparts, overall survival was greater for the TH+2 group (greater than 36 mo) than the TH-2 group (less than 12 mo). These studies demonstrate that T-cell leukemias in man arise from distinct T-cell subsets and that cell surface characterization of T-cell malignancies may provide useful clinical data related to prognosis.