The influence of bcl-2 oncogene expression on etoposide-induced apoptosis and clonogenic survival was investigated in five small cell lung cancer (SCLC) cell lines, three of which were bcl-2-expressing and two of which were non-bcl-2-expressing. The bcl-2-expressing lines displayed a lower apoptosis propensity than the non-bcl-2-expressing lines. When bcl-2-expressing cells were incubated in cystine/ methionine-free (CMF) medium, etoposide-induced apoptosis was restored to levels comparable to those seen in non-bcl-2-expressing lines. However, the endpoint of clonogenic survival after drug treatment did not display any consistent pattern that correlated with bcl-2 status. In addition, treatment of the two bcl-2-expressing cell lines with etoposide in CMF medium did not modify their clonogenic survival curves compared to treatment in regular medium. These results are consistent with the idea that bcl-2 expression modulates etoposide-induced apoptosis but not clonogenic survival.