A mAb, GL7, is described that reacts with a 35-kDa protein on subsets of activated mouse B cells as well as activated CD4+ and CD8+ peripheral T cells. In normal mice analyzed by flow cytometry, GL7 bound at low surface density to 0 to 9% of splenic B cells and 0 to 1% of splenic T cells. In contrast, GL7 bound at high density to a subpopulation comprising approximately 20% of TCR-bright thymocytes, and to B220+ cells in the bone marrow. The activation of B cells by various stimuli resulted in high levels of expression of the surface molecule identified by GL7 on up to 70% of B cells after 48 h; the remaining B cells expressed low or undetectable levels of this molecule, despite evidence of other activation-specific changes in cell-surface phenotype. The GL7-positive population of B cells induced by IL-5 stimulation exhibited high levels of both proliferative and IgM secretory activity, whereas the GL7-negative population showed little of either activity. Activation of splenic T cells with Con A for 48 h resulted in the expression of this determinant at high density on both CD4+ and CD8+ cells. GL7 thus appears to identify a previously uncharacterized cell-surface molecule expressed selectively on subpopulations of activated B and T cells as well as on discrete subpopulations of T and B lineage cells in vivo.