Site-directed mutagenesis was performed on His280 of the soluble interleukin-6 receptor (sIL-6R), which is probably a critical residue for the assembly of interleukin-6/interleukin-6receptor/gp130 complex. The mutant, His280Ile (named SLM97), had a higher binding affinity to interleukin-6 than wild type sIL-6R and exerted an inhibitory effect on the proliferation of Sko-007 human myeloma cells. Moreover, the activation of signal transducer and activator of transcription 3 (STAT3) induced by IL-6 in Sko-007 cells was also down-regulated in the presence of SLM97.