Bcl-2 and bax are cellular proteins that are important in the regulation of apoptosis. Overexpression of bcl-2 protein is associated with prolonged cell survival, whereas overexpression of bax correlates with increased apoptosis after injury. It has been suggested that the ratio of bcl-2 and bax determines a cell's susceptibility to apoptosis. We studied bcl-2 and bax expression by immunohistochemical methods in 46 cases of B-cel non-Hodgkin's lymphoma characterized by the Revised European-American Lymphoma (REAL) classification to determine whether expression of these two proteins correlated with the histological subtype or the predicted clinical behavior (indolent v aggressive). For each case, both the percentage of cells staining as well as the intensity of staining of bcl-2 and bax were recorded, and a bcl-2-bax protein ratio (BBPR) was calculated. Bax staining was identified in 100% of the lymphomas studied. In contrast, bcl-2 staining was seen in only 67%. Bcl-2 expression correlated with the subtype of lymphoma with positive staining in 100% of small lymphocytic lymphomas, 80% of follicle center lymphomas, 38% of diffuse large cell lymphomas, 33% of high-grade B-cell Burkitt's-like lymphomas, 0% of Burkitt's lymphomas, and 0% of B-cell lymphoblastic lymphomas. The BBPR of indolent lymphomas (mean, 1.8) was significantly greater than the BBPR of aggressive lymphomas (mean, 0.6) (P < or = .002). This suggests that bax and bcl-2 expression may be linked to biological behavior in non-Hodgkin's B-cell lymphomas.