Apoptosis and bcl-2 expression were characterized in leukaemic B cells during in vitro culture. Prior to culture, > 85% of cells from each B-CLL patient expressed high levels of bcl-2. Despite this, all leukaemic B-cell populations underwent apoptosis in vitro. Furthermore, bcl-2 was down-regulated such that the B cells displayed a bcl-2high and /or bcl-2low phenotype. However, the overall number of bcl-2-positive cells remained constant. We propose that although enhanced survival of leukaemic B cells in vivo is mediated by the sustained expression of bcl-2, it is apparent that additional mechanisms are capable of overriding the protective effect of bcl-2 when bcl-2 when bcl-2 is expressed at reduced levels.