The effectiveness of L-asparaginase as a chemotherapeutic agent in lymphoblastic leukemia has suggested that the growth of some neoplastic cells can be curtailed by limiting the availability of extracellular asparagine. An alternative method for depriving such dependent cells of an asparagine supply would be to prevent the transport of this amino acid across the cell membrane. Consequently, we have been studying the properties of asparagine transport systems in a variety of bacterial and mammalian cell types. These studies have particularly stressed a description of the substrate specificity properties of these systems. The ultimate objective of this project is to identify asparagine transport antagonists which may be clinically effective in retarding the growth of asparagine-dependent neoplastic cells. Accordingly, we propose to continue the examination of potential antagonists of asparagine transport in a variety of asparaginase-sensitive lymphomas and normal and leukemic leukocytes. We also plan to attempt the study of this system in various subcellular preparations in an effort to describe the mechanism of asparagine transport in greater detail.