This study identifies specific, high affinity GH-receptors (GH-R) in human hepatoma Hep G2 cells. The binding characteristics of GH-R in the Hep G2 cells are similar to those of human liver membranes, such as the high specificity for hGH, the binding affinity (K-a = 1.7 +/- 0.5 X 10(9) M(-1)) and the molecular weight of the membrane bound GH-R (apparent 125,000 and 71,000). In addition, lower molecular weight forms (similar to 94,000 and similar to 58,000) were identified as GH-binding protein (GH-BP) in Hep G2 conditioned medium, or following incubation of Hep G2 cells, in the presence of 10 mM N-ethylmaleimide for 90 min at 30 degrees C; the latter are presumed to be shed by a proteolytic cleavage of the GH-R. Exposure of Hep G2 cells to physiologic concentrations of hGH resulted in a concentration-dependent increase in H-3-thymidine incorporation, up to 48.4 +/- 7.9% above control. In summary, the demonstration of specific, high affinity GH-R in Hep G2 cells, as well as shedding of GH-BP, suggest these cells may provide a homologous human system to study the receptor-effector interrelationship of hGH and to further our understanding of hepatocyte production of soluble GH-BP.