The quality of life of 12 hemodialysis (HD) patients was assessed in a prospective, blinded, cross-over fashion before treatment with recombinant human erythropoietin (r-HuEPO) and at two different levels of hemoglobin (Hb, 9 and 12 g/dl) by means of an interviewer-based questionnaire, the sickness impact profile (SIP). Patients were matched into two groups with no significant difference for age, weight, Hb (6.3 ± 0.5, x ± SEM, group A, vs. 6.4 ± 0.9 group B), length of hemodialysis or number of years of prior transplantation. SIP was assessed prior to treatment, after reaching the first target Hb (Hb 9 g/dl group A, 12 g/dl group B), after 4 months at that target Hb and after 4 months at the alternative target Hb for each group. For all patients, there was a highly significant improvement in quality of life as assessed by lower SIP scores between the initial and second assessments. This was evident for the physical(8.9 ± 1.4 vs. 2.8 ± 1.0; p < 0.001) and psychosocial (14.9 ± 3.9vs. 4.4 ± l.l;p < 0.01) dimensions. Total scores (16.3 ± 2.4 vs. 5.7 ± 0.9; p < 0.001) showed similar changes, reflecting significant improvement in 10 of 12 possible categories between the first two assessments (p < 0.05 to p < 0.001). Improved scores were maintained but did not change appreciably after the 2nd assessment. There was no significant difference in any score (category, dimensional or total) obtained after 4 months at Hb 9 g/dl compared to those after the same period at Hb 12 g/dl. There was also no significant difference in scores between the two groups at any assessment. Results support an enhanced quality of life from r-HuEPO in HD patients which might not improve beyond a certain level of hemoglobin, as most benefits were evident at a Hb o