4‐1BB is a member of the TNF receptor family predominantly expressed on activated T cells, and binds an inducible ligand found on B cells, macrophages and dendritic cells. Whereas ligation of 4‐1BB has been shown to enhance response of purified CD8 T cells to mitogens, and to augment NK activity and generation of cytotoxic T lymphocytes in vivo, there are little direct data on 4‐1BB action during CD4 responses. Using pigeon cytochrome c‐presenting fibroblast antigen‐presenting cells transfected with 4‐1BB ligand (4‐1BBL), we show that engaging 4‐1BB on naive CD4 cells promotes proliferation, cell cycle progression and IL‐2 secretion, and suppresses cell death, all to a similar extent as B7‐1 engagement of CD28. In addition, 4‐1BBL synergizes with B7 and ICAM to enhance naive CD4 proliferation when antigen is limiting. 4‐1BBL alone, and to a greater extent with B7, also augmented IL‐2 secretion resting antigen‐experienced CD4 cells, as typified by T helper clones, whereas short‐term effector cells showed similar levels of proliferation and cytokine secretion regardless of whether 4‐1BB was engaged. A major role in augmenting IFN‐γ, IL‐4 or IL‐5 was not demonstrated. Blocking studies with activated B cells presenting antigen showed that 4‐1BB participates in promoting IL‐2 production by resting CD4 cells, confirming that 4‐1BBL can play a role in antigen‐specific CD4 T cell responses.