The reversible inhibition of DNA synthesis in mouse and hamster cells in vitro by l-canavanine, a structural analogue of l-arginine, is described. Inhibition of RNA and protein synthesis also occurs. Several lines of evidence are presented which support the concept that the inhibition of DNA synthesis is the result of the synthesis of an abnormal canavanylprotein required for DNA synthesis rather than a general, nonspecific inhibition of either RNA or protein synthesis. © 1969.