Serum soluble interleukin-6 receptor (sIL-6R) concentrations were measured in 52 patients with multiple myeloma (MM) and 24 normal controls, using a commercially available immunoenzymatic assay kit. Patients were staged according to the Bataille et al. myeloma staging system based on the levels of patients' serum beta 2-microglobulin and C-reactive protein. Twenty-one patients were at stage A of disease, 19 at stage B and 12 at stage C at the time of serum collection for sIL-6R determination. Serum sIL-6R concentrations ranged from 15 to 176 ng/ml with a mean of 64.8 +/- 35.9 ng/ml and a median of 58 ng/ml in the entire group of patients studied. These values were significantly higher than those of 34.4 +/- 13.4 ng/ml found in the controls (P < or = 0.001). Patients of stage C had higher sIL-6R levels (94.8 + 41.2 ng/ml) than patients of stage B (67.7 +/- 31.0 ng/ml) (P < 0.01), and markedly higher than patients of stage A (45.0 +/- 23.1 ng/ml) (P < 0.001). Serum levels of sIL-6R in patients with stage A disease did not differ statistically from those of the controls. A linear positive correlation was observed between serum levels of the receptor and the stage of MM (r = 0.539, P < 0.001). These data strongly suggest that serum sIL-6R concentrations correlate with the stages of MM and may be used as an indicator of the activity of the disease.