The soluble transferrin receptor (sTfR) is a parameter of erythropoietic activity and iron deficiency. Increased levels have also been described in hematological malignancies, especially in chronic lymphocytic leukemia (CLL). We investigated the value of sTfR in the assessment of tumor mass in 61 previously untreated CLL patients. Both hemolysis and iron deficiency were excluded. sTfR was measured nephelometrically (normal 0.81-1.75 mg/L). All Binet A patients had normal sTfR values (1.36+/-0.22 mg/L). In Binet B patients, the sTfR was increased (3.08+/-1.70 mg/L, p<0.0001) compared to Binet A patients. Binet B patients with normal sTfR had a small tumor load and no abdominal involvement. A further increase of sTfR in Binet C (3.75+/- 2.32 mg/L) was not significant compared to Binet B patients. sTfR values decreased or even normalized after successful treatment, whereas relapse or disease progression was associated with another increase of sTfR. The sTfR concentration directly reflects the tumor burden in CLL. Therefore, sTfR may be of clinical value in monitoring disease activity, response to treatment and disease progression.