The relationship between serum ferritin and tissue iron was investigated in 26 dialysis patients (17 hemodialysis patients. 9 chronic peritoneal dialysis patients) with anemia (median hemoglobin 74 g/l, range 56-92 g/l). Serum ferritin ranged from 18 to 9,435 micrograms/l (median 450 micrograms/l). Tissue iron was assessed in the liver biopsies of 4 hemodialysis patients with iron overload (serum ferritin 1,150-9,435 micrograms/l), in the muscle biopsies of 5 patients with serum ferritin 170-9,435 micrograms/l, and in bone marrow aspirations (semiquantitative assessment). The mean liver iron concentration was 15.4 +/- 8.0 micrograms Fe/mg protein (mean +/- SD), which is similar to that previously found in patients with untreated idiopathic hemochromatosis. Four patients with serum ferritin 170-620 micrograms/l had muscle iron concentrations (0.33 +/- 0.10 microgram Fe/mg protein) similar to those found in controls (0.23 +/- 0.10, means +/- SD). One patient with serum ferritin 9,435 micrograms/l had a markedly increased muscle iron concentration (1.3 micrograms Fe/mg protein). The bone marrow iron was assessed as negative in 3 patients (serum ferritin 44-85 micrograms/l), positive in 8 (serum ferritin 18-379 micrograms/l), increased in 11 patients (serum ferritin 222-4,210 micrograms/l), and was markedly increased in 2 patients (serum ferritin 4,550 and 9,435 micrograms/l). Bone marrow iron correlated significantly with serum ferritin concentrations (spearman rank correlation coefficient rho = 0.89, p < 0.001). These results show that in dialysis patients with a stable iron balance and unstimulated erythropoiesis, i.e., patients without erythropoietin treatment and parenteral iron, serum ferritin is a useful indicator of iron stores. Our findings also suggest that the relationship between tissue iron and serum ferritin levels in end-stage renal disease is altered, i.e. a relative increase in serum ferritin levels unrelated to iron stores is observed in dialysis patients.