Objective Oral iron is poorly absorbed in chronic dialysis patients. We tested the hypothesis that a superpharmacologic dose of iron sulfate (260 mg elemental iron) administered on an empty stomach results in significant iron absorption in these patients. Design A prospective open controlled trial. Setting Outpatient department of a university hospital. Patients Nine stable chronic peritoneal dialysis (PD) patients and seven normal control subjects. Method All subjects ingested a single dose of 4 tablets of iron sulfate (260 mg elemental iron total) in the morning while fasting. Outcome Measures Serum iron concentrations at baseline, and at 2 and 4 hours after the oral dose were compared between the two groups. Results The control group showed a significant rise in mean [± standard error (SE)] serum iron concentration, from a baseline value of 76.5 ± 7 μg/dL to 191 ± 10.5 μg/dL at 2 hours and to 190 ± 24 μg/dL at 4 hours. This result represents a percentage rise of 164% ± 32% at 2 hours and 152% ± 28.5% at 4 hours. In the PD patients, a significant rise in serum iron concentration was also seen, from a baseline value of 64 ± 8 μg/dL to 130 ± 3 μg/dL at 2 hours and 111 ± 18 μg/dL at 4 hours. This result represents a percentage rise of 105% ± 29% at 2 hours and 77% ± 23.5% at 4 hours. However, the absolute change in serum iron concentration in PD patients at 2 and 4 hours was approximately equal to 50% of the change in control subjects at those time points. None of the PD patients experienced gastrointestinal side effects; 4 control subjects experienced mild side effects. Conclusion Despite impaired oral iron absorption in chronic dialysis patients, a large pharmacologic dose given orally can result in significant iron absorption and may prove to be a more efficient means of oral iron supplementation therapy in these patients.