The discovery of lymphokines stemmed from their ability to promote T-lymphocyte proliferation in vitro. Even after 20 years of intensive investigation, crucial aspects remain to be clarified about the role of specific lymphokines in T-cell proliferation and the biochemical mechanisms by which they play these roles, particularly in vivo. The present review focuses on conventional populations of TCR(alpha)beta T cells. Older findings and new insights into the function of specific lymphokines in T-lymphocyte proliferation in vivo are summarized along with unanswered questions raised by these observations. Vital contributions of lymphokines to clonal proliferation arise from two processes: the protection of cells against apoptosis and the activation of cell cycling. Findings are underscored indicating that the activity of a particular lymphokine depends on the subset of T cells (CD4 vs. CD8; naive vs. memory) to which it binds, and that point to potential pitfalls of extrapolating from tissue culture-adapted models to the regulation of T cells in vivo. After summaries of signaling mechanisms related to the proliferative activity of lymphokines, recent findings are highlighted suggesting that such signaling is a regulated and plastic process rather than one fixed schema of action.