The monocyte-derived cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), are central regulators ofthe immune response, but the physiologic stimuli for their release remain lagely undefined. Engagement of three monocyte glycoproteins, LFA-3, CD44, and CD45, by specific monoclonal antibodies immobilized on plastic induced TNF-α and IL-1β release. In addition, TNF-α was released when monocyte LFA-3 bound immobilized, purified CD2, which is its physiologic receptor. Thus, a receptor-ligand interaction that mediates cell-cell adhesion can transmit the necessary signals for the release of monokines.