Although knowledge about genes involved in cell growth has increased, how cells fulfill their demands of membrane components required for proliferation and differentiation is unclear. c-Fos is capable of activating enzymes responsible for phospholipid synthesis (PLS),in distinct cell types (Bussolino et al., 2001). It associates to the endoplasmic reticulum (ER) and activates PLS in the cytoplasm, independently of its genomic AP-1 activity (Gil et al., 2004). In lymphocytes, c-Fos is detected both in the cytoplasm and the nucleus at early times after Con A stimulation and remains associated to ER long after the genomic program has been triggered. In this work, we investigated if c-Fos also activates PLS in lymphocytes. To this aim, homogenates prepared from non-stimulated (NSH), 48h-stimulated splenocytes (SH) or stimulated membrane fraction (SM) were examined for in vitro phospholipid labeling. Incorporation of ³²P from ³²P-ATP into phospholipids was measured. An increased PLS was observed in stimulated lymphocytes, mainly in the membrane fraction (NSH: 318.4±121.4; SH: 1177.7±698.4; SM: 7055.5±4428.2 cpm). When membranes were stripped with 1M KCl to remove non integral associated c-Fos (M-KCl), PLS increased in the presence of recombinant c-Fos (M-KCl +Fos: 22745.5±1341.4 cpm), and it was not observed in M-KCl without addition of recombinant c-Fos (M-KCl-Fos: 7847.2±1389 cpm). These results are a direct confirmation that c-Fos participates in PLS in immune system cells.