SummaryA range of pharmacological agents with defined effects on cell metabolism was used to determine the metabolic requrements of three cell adhesion systems: aggregation of cells from the sponge,Ophlitaspongia tennis;fibronectin‐induced adhesion of fibroblasts to subsiraia and anin vitromurine thymocyic‐macrophage interaction. Cell adhesion in all three systems was found to have similar metabolic requirements, implying that the mechanism of cell adhesion has been conserved through evolution. In fact, based on analysis of F‐actin organization in throblasts, all of the pharmacological agents that inhibited cell adhesion were found to disrupt the cytoskeleion, suggesting that the cytoskeieton plays a central role in the adhesion process, presumably via redisiribution of cell surface molecules. This concept was supported by the finding that the same drugs that inhibited cell adhesion inhibited anti‐lg‐induced redistribution of surface Ig on B tymphocytes. The drug Inhibition studies also revealed that two drugs, bromophenacyl bromide (BPB) and norditiydroguaiaretic acid (NDGA), that were previously believed lo be selective inhibitors of arachidonic acid synthesis and metabolism, are also potent disruptors of the cyioskeleton.