We describe a systematic examination of ornithine decarboxylase activity in 120 colonic mucosal samples which were obtained from 20 subjects without colonic disease to establish the normal mean and standard deviation from proximal to distal colon. Ornithine decarboxylase activity was determined by releasing CO2 from DL-[1-14C]ornithine. The mean ornithine decarboxylase levels (CO2 liberated) ranged from 0.26 +/- 0.08 nmol/h.mg protein in the caecum to 0.44 +/- 0.16 nmol/h.mg protein in the rectum. There was no difference between sex and age. Ornithine decarboxylase was not stimulated by guanosine 5'-triphosphate. alpha-Difluoromethylornithine showed an ornithine decarboxylase inhibition of 97.1%. Ornithine decarboxylase activity can be measured with reliable precision and reproducibility. The knowledge of the normal range of ornithine decarboxylase activity in normal human colonic mucosa is necessary for the determination of ornithine decarboxylase activity in pathological findings, especially in malignant transformation.