Ornithine decarboxylase (ODC) is the key enzyme of polyamine synthesis. The physiological activity of ODC is associated with cell proliferation, and high ODC activities are encountered in rapidly growing cancer cells. We have cloned a cDNA for a novel human protein that is 54% identical to ODC and 45% identical to antizyme inhibitor (AZI). mRNA for ODC-paralogue (ODC-p) was found only in the central nervous system and testes, suggesting a role in terminal differentiation rather than cell proliferation. ODC-p occurs at least in eight alternatively spliced forms. In vitro translated ODC-p did not decarboxylate ornithine, whereas, in vivo, one splice variant exerted modest ODC-like activity upon expression in COS-7 cells. ODC-p has a unique mutation in cysteine 360, where this ornithine decarboxylase reaction-directing residue is substituted by a valine. This substitution might lead to an enzymatic reaction that differs from typical ODC activity. ODC-p might also function as a brain- and testis-specific AZI.