Overexpression of c-Myc in murine B lineage cells is associated with a polyclonal pre-B cell expansion as well as development of pre-B or B lymphoblastic lymphoma (LL) accompanied by leukemia, which mirrors the clinical features of childhood LL. Of interest, Max overexpression attenuates aberrant growth of B cells triggered by c-Myc. However, the clinical significance of Max in human lymphoid tissue remains to be clarified. In the present studies, we studied the expression of the c-Myc and Max proteins in normal lymph nodes and in childhood LL. In normal lymph nodes, c-Myc protein was expressed by the majority of cells in germinal center and marginal zone, but Max protein was expressed only by some of them. In contrast, c-Myc and Max were absent in mantle zone. Cells positive for c-Myc and Max expression in LL were 70.6 +/- 19.8% and 47.3 +/- 32.4%, respectively, determined by immunohistochemical staining using paraffin blocks from 23 cases of childhood LL. The survival of children with LL showing higher Max expression (> or = 30%) was significantly greater than that of lower expression (< 30%; P = 0.0027 using the Mantel-Cox test). These results suggest that Max protein may affect prognosis of childhood LL.