Objective: Chronic hepatitis C (CHC) in hemodialysis patients has not been thoroughly investigated, despite its high frequency. The present comparative study aims to highlight the histological features of CHC and its association with putative pathogenetic parameters in this specific group of patients. Method: Sixty-one biopsies of hemodialysis patients and 326 biopsies from the general population with CHC were comparatively evaluated for the severity and specific histological features of CHC. Results were examined in relation to age, time of dialysis, viral load and genotype. Results: Patients on hemodialysis were older than patients of general population (p=0.031), showing a similar genotype distribution (p=0.328) and lower viral loads (p=0.001). CHC on hemodialysis was significantly milder according to stage (p=0.033), activity and its parameters (p<0.001). Significantly reduced was also the frequency of lymphoid aggregates (p< 0.001), bile duct damage (p<0.001) and steatosis. (p=0.033). Severity of hepatits was not associated with time on hemodialysis. In multivariate analysis the differences were independent of age, which was associated with more severe disease. Steatosis was associated with hemodialysis duration and age. Conclusion: CHC in hemodialysis patients is significantly milder than in general population. Limited necroinflammatory activity and absence of immune mediated lesions are indications of defective immune response although involvement of low viral load cannot be overlooked.