Bacterial contamination of dialysate may enhance cytokine production in hemodialysis. The authors tested the hypothesis that C-reactive protein and interleukin-6 (IL-6) may be linked in a large group of patients exposed to backfiltration of dialysate over a long period of observation. Plasmas stored in a recently published multicenter study were reevaluated. Plasma C-reactive protein and IL-6 concentrations in patients with chronic uremia undergoing hemodiafiltration, which is known to be associated with backfiltration (Group II, 12 patients), were compared with those found in patients treated with a modified hemodiafiltration modality without backfiltration (Group I, 16 patients), and in patients shifted from one modality to the other (Group III, 27 patients), and in 10 patients on hemodialysis (Group IV) in a 1 year multicenter study. Plasma C-reactive and IL-6 both increased significantly (p < 0.002), but slowly (after 8 months) in Group II compared with I, and during the 4 month period in hemodiafiltration with backfiltration in Group III. Backfiltration of dialysate with a moderate to low degree of contamination may enhance synthesis of cytokine and C-reactive protein in the long term. Thus, the relevance for dialytic strategies aiming at improving dialysate quality or at reducing backfiltration is highlighted.