Numerous investigations have shown that activation of biosynthesis and accumulation of polyamines in tissue accompany cell growth. It is not certain, however, whether the increase in the polyamine levels in these tissues causes the elevated rate of protein synthesis, or it is the elevated rate of protein synthesis that causes the increase in the polyamine levels in these tissues. One way to determine the role of polyamines in proliferating tissue would be to block their biosynthesis and determine whether this would cause inhibition of cell growth. The inhibition of ornithine decarboxylase seems to be the most logical route to block polyamine biosynthesis because (1) the decarboxylation of ornithine appears to be the rate-limiting step in the biosynthetic pathway of polyamines and (2) the formation of putrescine from ornithine takes place in regenerating tissue but not in normal tissue. In these studies we intend to synthesize analogs of ornithine as potential inhibitors of the enzyme ornithine decarboxylase (4.1.1.17). Four structural analogs of ornithine are proposed. These are: a- methyl, a-hydrazino, and a-aminoketone analogs and Na-(Pyridoxyl-5'- phosphate)-L-ornithine. Similar modifications of other amino acids have afforded potent inhibitors of these amino acids decarboxylases in the past. The synthesized compounds will be tested as inhibitors of the ornithine decarboxylase activity in liver homogenates obtained from rats after partial hepatectomy. The preparation of a specific inhibitor of ornithine decarboxylase might afford a growth inhibitor selective to proliferating tissue.