Imatinib mesylate inhibits phosphorylation of molecules participating in cellular signaling. To identify imatinib mesylate–sensitive intracellular signaling pathways we measured the levels of phosphorylation of Lck and ERK1/2, both associated with TCR-mediated signaling. We exposed PHA-stimulated T cells to imatinib mesylate (10 μM) and found that the drug did not affect the levels of Lck protein, but it inhibited Tyr505 phosphorylation. Similarly, imatinib mesylate inhibited phosphorylation of ERK1/2.