Phosphoinositide 3-kinases (PI 3-Ks) phosphorylate the d3-hydroxyl position of phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)] resulting in the generation of the 3'-phosphoinositide lipid PtdIns(3,4,5)P(3). PI 3-Ks are activated by a diverse set of receptors that play a role in determining T-cell function. It now seems that leukemic T cells, which are widely used as models for T-cell biology, show constitutive activation of PI 3-K-mediated signal-transduction pathways. Hence, studies of the role of PI 3-K in T-cell biology using leukemic cell lines might have misinterpreted the importance of this pathway for T-cell signal transduction.