The transcription factor AP-1, made up of dimers of Fos and Jun proto-oncogene products, is involved in distinct cellular processes, including cell proliferation, differentiation and apoptosis. In this study, we have used mice in which both copies of the c-fos gene were disrupted by targeted mutagenesis in order to analyze how the apoptotic response was affected in these mice. We prepared primary cultures from the lymphoid organs, spleen and thymus, obtained from both wild-type and c-fos -/- mice and analyzed the induction of apoptosis in these cultures in the absence and presence of etoposide, an inducer of apoptosis in distinct cell types. Primary cultures from both organs, spleen and thymus, isolated from wild-type mice underwent apoptosis after 3 and 6 h of culture, respectively. Addition of etoposide enhanced the apoptotic response and c-fos mRNA levels in both spleen and thymic cells. Nevertheless, we found that induction of apoptosis in primary cultures of cells obtained from spleen and thymus of c-Fos-deficient mice was practically identical to that observed in wild-type mice. These results demonstrate that c-Fos is not essential for apoptosis and that cells lacking c-Fos may undergo normal apoptosis.