Interleukin (IL)‐15 is a newly described cytokine with properties similar to IL‐2. Even though it does not share sequence homology with IL‐2, both cytokines bind to the same receptor with the noted exception of a cytokine specific α‐chain. In this study the authors compared IL‐2 and IL‐15 to determine their ability to rescue short term activated lymphocytes (phytohaemagglutinin stimulation of peripheral blood mononuclear cells for 6 days, followed by expansion in medium containing IL‐2 for 2 days) from apoptotic cell death. The authors found that both IL‐2 and IL‐15 can inhibit induction of apoptosis in this experimental model with similar time and dose kinetics. On mRNA or protein levels induction of pro‐ and anti‐apoptotic gene products like fasL, bcl‐2, or bax with minor effects on fas/Apo‐1 or bcl‐xL was observed under culture conditions with both IL‐2 and IL‐15. Next, it was found that phytohaemagglutinin (PHA) blasts were less responsive (in terms of cellular proliferation and prevention from apoptosis) to IL‐2 if signals through the α‐chain were blocked, with no effect on β‐chain specific monoclonal antibodies (MoAb). By contrast, IL‐15 was less effective in induction of cellular proliferation and prevention of apoptosis if IL‐2R β‐chain specific MoAb were added to cell cultures. Testing intracellular signalling induced by IL‐2 or IL‐15, the authors found identical changes in tyrosine phosphorylation patterns in PHA blasts cultured in medium or under IL‐2 or IL‐15 stimulation. By contrast, they found consistent differences if PHA stimulated peripheral blood mononuclear cells (PBMC) were expanded in medium containing IL‐15 (instead of IL‐2). These IL‐15 expanded PHA blasts showed a significantly increased percentage of apoptosis after growth factor withdrawal. Furthermore, IL‐2 was more efficient than IL‐15 in rescuing IL‐15 expanded PHA blasts from apoptosis. In IL‐15 expanded PHA blasts expression of IL‐2R α‐chain was lower than that in IL‐2 expanded PHA blasts. A model presenting a differential role for IL‐2 and IL‐15 in inhibition of apoptosis in vivo is discussed.