IL‐2 is known to play a critical role in regulating T lymphocyte proliferation. We show here that IL‐2 also provokes an instantaneous and sustained membrane ruffling in cloned human or murine T cells as well as in lectin‐activated peripheral blood lymphocytes. In the IL‐2‐induced lamellipodia, tubulin is depolymerized whereas actin is strongly polymerized, forming caps. IL‐2‐induced membrane ruffling is protein kinase C (PKC) independent, as judged by the absence of effects of bisindolylmaleimide, an efficient inhibitor of all PKC isoforms. The formation of lamellipodia by IL‐2 is blocked by wortmannin and LY294002, two inhibitors of phosphoinositide 3‐kinase (PI3‐kinase). Moreover, expression in murine T cells of an inactive form of PI3‐kinase inhibits IL‐2‐induced membrane ruffling, whereas expression of a constitutively active p110 increases the basal membrane ruffling. Rac is also involved in IL‐2‐induced membrane ruffling since an inactive form of Rac (N17rac) blocks the IL‐2‐induced lamellipodia, whereas the constitutive form of Rac (Val12rac) can also lead to membrane ruffling. In the signaling cascade, Rac is downstream of PI3‐kinase since constitutive membrane ruffling in Val12rac cells is insensitive to wortmannin. Thus, through a signaling cascade involving PI3‐kinase and Rac, IL‐2 can induce profound alterations of the T cell cytoskeleton, a phenomenon which might be of importance for T cell physiology.