Type 1 and type 2 cloned T helper (Th) cells are believed to require different antigen-presenting cell (APC)-derived costimuli for proliferation. In the case of Th1-cloned T cells, CD28 signaling costimulates production of autocrine interleukin 2 (IL-2). Th2 cells produce their autocrine growth factor, IL-4, without costimulation, but require APC-derived costimuli, or IL-1, to respond to IL-4. Here we demonstrate that engagement of CD28 on Th2 cells with anti-CD28 antibody or with APC-associated B7 costimulates Th2 responsiveness to IL-4 but does not affect IL-4 or IL-2 production by Th2 cells. Costimulation of Th2 cells via CD28 appears to involve the induction of IL-1 production by Th2 cells, which acts in an autocrine fashion to induce IL-4 responsiveness. These results suggest that CD28-induced costimulation plays an important role in responses mediated by both types of Th cells.