In human body fluids a soluble form of the interleukin-6 receptor (sIL-6R) has been found which together with interleukin-6 (IL-6) acts agonistically on cells expressing the signal transducer gp130. The means by which the sIL-6R is removed from the circulation is unknown. Here, we show that a complex of 125I-labelled recombinant sIL-6R and IL-6 is internalized by MDCK cells stably transfected with gp130 and by human hepatoma cells HepG2 that endogenously express the IL-6R and gp130. We further show that most of the internalized sIL-6R is degraded within lysosomes. Our studies suggest that cells expressing gp130 are capable of endocytosing an IL-6/sIL-6R complex, thereby removing both from the circulation.