The recently solved X-ray structure of the extracellular portion of the interleukin-6 (IL-6) receptor (IL-6R) revealed an IL-6R dimer in the crystal lattice which probably represents a physiological dimer. Performing coprecipitation experiments with two differently tagged IL-6R variants expressed in COS-7 cells, we show that an IL-6R dimer exists in the plasma membrane in the absence of IL-6. Ligand binding does not seem to affect the dimerization status. When lysates of COS-7 cells expressing only one of the IL-6R variants are mixed, spontaneous dimerization occurs. Thus, the IL-6R dimer observed in the crystal structure represents a physiologically occurring phenomenon.