Oxidative stress plays an important role in the cardiovascular complications in end-stage renal disease (ESRD) patients on long-term hemodialysis (HD). Heme oxygenase-1 (HO-1) inhibits inflammatory events and protects against oxidative stress and endothelial injury. Therefore, we followed the effects of single HD sessions on HO-1 expression. A competitive reverse transcriptase PCR method was used to estimate HO-1 induction before and immediately after HD and 48 h later in 17 young uremic patients. We also measured the concentrations of plasma hemoglobin and bilirubin as indicators of hemolysis, the ferroxidase activity, and the erythrocyte-derived reduced and oxidized glutathione levels as oxidative stress markers, and the homocysteine levels as an independent risk factor. We found significant differences in HO-1 expression patterns in the patients, depending on the duration of HD treatment. Short-term HD [ n=7, median 19 months (9, 29 quartiles)] resulted in an elevated HO-1 expression, which was not further upregulated during HD. Long-term HD [ n=10, median 97 months (53, 150 quartiles)] led to downregulation of baseline HO-1 expression in ESRD patients. In these patients, a single HD session results in erythrocyte injury and a transient one- to five-fold elevation of HO-1 expression. The chronic downregulation of the baseline expression of HO-1 in long-term HD patients resulted in recurring oxidative stress during each HD session, which may contribute to accelerate the progression of atherosclerosis.