The immunologic and clinicopathologic features of common acute lymphoblastic leukemia antigen (CALLA)-positive and CALLA-negative T-acute lymphoblastic leukemia (ALL) and of CALLA-positive non-T, non-B ALL (common ALL) of childhood were compared. Twenty-seven percent of children with T-ALL had blasts that expressed CALLA. This expression was not associated with a significantly different incidence of expression of sheep erythrocyte-rosette receptors, glucocorticoid receptors, peanut agglutinin receptors, or T-cell antigens. CALLA-positive T-cell blasts were more likely to express a p24 leukemia-associated antigen (CD9, 50% versus 8%) and Ia antigens (39% versus 8%) than were CALLA-negative blasts. Patients with CALLA-positive and CALLA-negative T-ALL had similar clinicopathologic features at diagnosis. In contrast, compared to patients with common ALL, patients with CALLA-positive T-ALL were older, had higher leukocyte counts, and an increased incidence of splenomegaly, lymphadenopathy and mediastinal mass, similar to patients with CALLA-negative T-ALL. Patients with CALLA-positive T-ALL were more likely to achieve a complete remission (95% versus 83%, P = 0.055) and tended to have an increased duration of event-free survival (P = 0.07) than did patients with CALLA-negative T-ALL. The expression of T-cell antigens is more important than the expression of CALLA in defining biologically similar subgroups of childhood ALL. Preliminary evidence suggests that within T-ALL the expression of CALLA may be prognostically important.