The cytokine CD137, a member of the TNF receptor family, is expressed by T cells and regulates activation and proliferation of these cells. The CD137 ligand (CD137L) is expressed by antigen-presenting cells including macrophages, but also on various carcinoma cells. CD137/CD137L interaction plays a central role in sustaining T cell and macrophage activation, i.e. in antitumour immunity. The present study was designed to investigate whether CD137 and CD137L protein levels are altered in colorectal tumours compared with paired normal tissues. The CD137 and CD137L plasma levels from patients with colorectal cancer were also examined. Collectively, we noted a significantly lower CD137L level in cancerous tissue compared with paired normal tissue, and the difference in CD137L protein level was significantly lower in the colon cancer subgroup compared with paired normal colon tissue. On the other hand, we found an elevated CD137 protein level in the rectal cancer subgroup compared with paired normal rectal tissue. Patients with a tumour localised in the colon revealed significantly higher soluble CD137 protein concentration in the plasma than patients with a tumour localised in the rectum, and there was a tendency toward a higher concentration of CD137L protein in the plasma from patients with tumour localised in the colon. Moreover, the plasma concentrations of CD137 and CD137L proteins were strongly and significantly correlated. The different expression levels of CD137 and CD137L in the colon and rectum may reflect divergent mechanisms involved in the pathogenesis of colorectal cancer and lead to dissimilar protective immunity.