Intracellular signal transduction following the extracellular ligation of a wide variety of different types of surface molecules on leukocytes involves the activation of protein tyrosine kinases. The dependence of successful intracellular signaling on the functions of the nontransmembrane class of protein tyrosine kinases coupled with the cell type-specific expression patterns for several of these enzymes makes them appealing targets for therapeutic intervention. Development of drugs that can interfere with the catalytic functions of the nontransmembrane protein tyrosine kinases or that can disrupt critical interactions with regulatory molecules and/or substrates should find clinical applications in the treatment of allergic diseases, autoimmunity, transplantation rejection, and cancer.