The effects of the calmodulin antagonist trifluoperazine on the development of colon tumors induced by azoxymethane (AOM), and on the labeling index of the colon mucosa and the activity of ornithine decarboxylase (ODC) in the colon wall were investigated in Wistar rats. Prolonged administration of trifluoperazine significantly reduced the number of colon tumors in week 35. Administration of trifluoperazine caused a significant decrease in the labeling index of the colon mucosa and the AOM-induced ODC activity in the colon wall during administration of the carcinogen, but not after its cessation. A possible mechanism of inhibition of colon carcinogenesis by trifluoperazine could be its inhibition of AOM-induced increase in ODC activity of the colon wall with consequent suppression of cell proliferation in the colon.