The roles of Bcl-2 protein and the protein ratio of Bcl-2/Bax in regulating cell growth in various lymphoma cell lines were examined. A dose-dependent decrease in Bcl-2 protein expression was observed in the different lymphomas incubated with lipid-incorporated bcl-2 antisense oligonucleotides (L-bcl-2). Growth inhibition was observed in a transformed follicular lymphoma (FL) cell line, which has the t(14;18) translocation and Bcl-2 protein overexpression. One of the mechanisms by which L-bcl-2 growth inhibition is mediated in these transformed FL cells might be through apoptotic induction, because the treated cells had an increased apoptotic index and showed the typical DNA fragmentation. These studies indicate that Bcl-2 protein is critical in the growth regulation of transformed FL cells. L-bcl-2 did not induce growth inhibition in lymphoma cells not expressing Bcl-2 or Bax protein. Thus, the protein ratio of Bcl-2/Bax may also be important in regulating the growth of these lymphomas.