Interleukin-6 is a multifunctional cytokine participating in the regulation of several immunologic and other cell-physiological phenomena. It acts via a receptor consisting of two components, that besides the ligand-specific chain also contains a second component of 130 kD (gp 130). The soluble form of the ligand-specific component of this receptor was shown to occur physiologically in body fluids and -following the binding of interleukin-6-to be capable of associating with the membrane-bound receptor component and inducing signal-transduction. We studied the possible differences between the effects of interleukin-6 exerted via membrane-bound or soluble receptors on HepG2 human hepatoma and primary rat hepatocyte cultures. We used two methods to study the action of interleukin-6: the mRNA expression of the protooncogene junB as an early marker, and the protein production of fibrinogen as a late one. The effect of interleukin-6 on both cell types examined with both methods used was lower via the soluble than the membrane-bound receptor. In addition, the soluble receptors alone (without interleukin-6) could induce the expression of the junB gene. Considering the wide-spread biological and pathological activities of interleukin-6 these phenomena could have some role in the pathogenesis of some diseases.