Summary: Adapter proteins regulate leukocyte signal transduction through recruitment of effector molecules to multiprotein complexes. Recent studies in Adhesion and Degranulation promoting Adapter Protein (ADAP)-deficient mice have established that the cytoplasmic phosphoprotein ADAP is required for optimal, mature T-cell proliferation. Furthermore, ADAP plays a key role in T-cell antigen receptor (TCR)-mediated ‘inside out’ signaling leading to integrin activation and to enhanced cellular adhesion to integrin ligands. ADAP associates physically with molecules known to play roles in the regulation of TCR-stimulated actin polymerization. These associations support the hypothesis that ADAP functions in actin cytoskeletal reorganization leading to cellular adhesion and activation.