Summary:Peripheral blood lymphocytes obtained from cancer patients receiving interleukin‐2 (IL‐2) on two separate clinical protocols were evaluated for their in vitro responses to IL‐2, alloantigens, and PHA. IL‐2 in vivo induced enhanced in vitro proliferative responses to IL‐2 and diminished in vitro proliferative responses to phytohemagglutinin (PHA) and alloantigens. Alloinduced cytotoxic T cell responses were also depressed following in vivo IL‐2. We examined the kinetics of the in vitro proliferative response to PHA and IL‐2 and found that while the response of lymphocytes primed in vivo with IL‐2 to PHA was depressed at all times during the 2 week in vitro exposure, the response to IL‐2 peaked earlier and higher than did the response to IL‐2 by lymphocytes obtained prior to IL‐2 therapy. These contrasting effects on an‐tigen‐induced T cell responses vs. IL‐2 induced nonspecific proliferative and cytotoxic responses suggest the importance of dose and timing of IL‐2 administration when used to enhance antigen‐specific T cell responses or as an immune enhancing agent combined with vaccines.