Interleukin-13 (IL-13) is a T-cell-derived cytokine that displays homology with IL-4 and shares some of its biologic functions. We investigated the effects of IL-13 on normal human B-cell precursors (BCP) and their malignant counterparts in B-lineage acute lymphoblastic leukemia (BCP-ALL). IL-13 inhibited growth of CD19+ slg- normal BCP cultured in the presence or absence of bone marrow accessory stromal cells and IL-7. In addition, IL-13 inhibited proliferation of blasts isolated from leukemic patients and cells from established BCP-ALL lines. Differences were observed in a number of cases with respect to growth inhibition in response to IL-13 and IL-4. These results suggest heterogeneity in the expression of IL-13 and IL-4 receptors in B-cell ontogeny. Growth-inhibition by IL-13 could be reverted by anti-IL-4 receptor antibody, indicating that the IL-13 and IL-4 binding chains can be closely associated on BCP. We further showed that the inhibitory effect of IL-13 results from decreased cell-cycle activity. Finally, whereas IL-13 induced CD23 expression on BCP-ALL cells, it did not promote differentiation into slg+ B lymphocytes.