The enteric nerve plexus in the colon was investigated in rats with chemically induced colonic adenocarcinoma. Tissue specimens from the colons of four group rats, namely controls, treated animals without development of colonic macro- or microscopic changes, rats with dysplasia and lymphoid hyperplasia, and rats with colonic adenocarcinoma were studied using immunocytochemistry, and quantified by computerized image analysis. No morphometeric changes were found in the treated rats regarding the myenteric and submucosal ganglia, with the exception of nitric oxide synthase (NOS), where the number of nerve cell bodies/ganglia was reduced in the myenteric ganglia in rats with both lymphoid hyperplasia and dysplasia, and carcinoma. The relative volume density of protein gene product (PGP) 9.5-immunoreactive (IR) nerve fibres was higher in the muscularis propria in rats with lymphoid hyperplasia and dysplasia, and carcinoma. However the relative volume density of PGP 9.5-IR nerve fibres was higher in the submucosa in rats with carcinoma only. The relative volume density of substance P- and VIP-IR nerve fibres was significantly higher in the muscularis propria in rats with colonic carcinoma. The relative volume density of NOS-IR nerve fibres was significantly decreased in both muscularis propria and submucosa in rats with lymphoid hyperplasia and dysplasia, and carcinoma. These findings imply that regulatory signals of the enteric innervation may be involved in the pathogenesis of colorectal cancer.