Polyamine biosynthetic activity was assessed in various colorectal tissue samples consisting of noninvolved mucosa, benign adenomatous polyps and adenocarcinomas taken at surgery from a total of 40 patients. Ornithine decarboxylase (ODC) displayed a gradient of enzyme activity (i.e., adenocarcinoma greater than polyps greater than mucosa) which seemed to correlate positively with the neoplastic status of the tissue. In 10 of the patients, samples were obtained for all three tissue types. Five of these exhibited a clear repetition of the trends in enzyme activity seen with the mixed patient tissue sampling whereas the remainder differed by having the highest ODC activity in the polyps. In nine of the ten cases, ODC activity was substantially lower in the mucosa than in either of the neoplastic lesions. Trends in enzyme activity were the same for tissues obtained from either the colon or rectum. The ODC activity in adenocarcinomas could not be correlated with histologic differentiation, stage or site of the disease, however, in samples from female patients (all postmenopausal) the activity was elevated over normal mucosa to a greater extent (ten-fold) than in male patients (seven-fold). S-adenosylmethionine decarboxylase activity was assessed in 27 of the 40 patients and found to follow the same distribution as ODC; however, the mean value differences +/- SEM between tissues were less distinct. In general, tissue polyamine pool analysis of these same specimens reflected the levels of ornithine and S-adenosylmethionine decarboxylase activities. Overall, the data reveal an increase in polyamine biosynthetic activity in colorectal neoplasms, relative to surrounding mucosa, which may correlate with (1) progression of the neoplastic process, (2) the proportion of proliferating cells, (3) the rate of cell proliferation, or (4) a combination of two or all of these possibilities.