Activation of lymphocytes through their antigen receptors leads to mobilization of intracellular Ca²⁺ ions. This process requires expression of SLP adaptors and involves phosphorylation of phospholipase C‐γ isoforms by the Tec‐related protein tyrosine kinase Btk in B cells and Itk in T cells. The SH2 domain of Btk and Itk is essential for phospholipase C‐γ phosphorylation and mutations in this domain lead to the X‐linked agammaglobulinemia immuno deficiency in humans. Here we show that, in contrast to SH2 domains from other signaling proteins, the Btk and Itk SH2 domains exhibit a restricted binding specificity. They bind selectively to tyrosine‐phosphorylated SLP‐65 and SLP‐76 in activated B and T cells, respectively. Our findings suggest that Btk / Itk and phospholipase C‐γ both bind via their SH2 domain to phosphorylated SLP adaptors, and that this association is required for the activation of phospholipase C‐γ.