The polyamines are known to be essential for cellular proliferation. Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the synthesis of these amines, and activity is elevated in colorectal tumors and polyps. Two ODC genes (designated ODC1 and ODC2) were localized by somatic cell hybridization and in situ techniques to 2p25 and 7q31-qter, respectively. Investigation of the expression of ODC in colorectal neoplasia reveals a consistent increase in mRNA expression compared with normal adjacent mucosa and control mucosa, ranging from 1.3- to 12.2-fold. No amplification of the loci was seen. Comparison of ODC mRNA expression with ODC activity from the same samples revealed no direct correlation, suggesting that regulation of ODC in this system occurs at the posttranscriptional level.