The actions of growth hormone (GH) are mediated through a cell surface cytokine receptor. We have previously demonstrated that naturally occurring truncated membrane bound GH receptors (GHRs) can block GH receptor signaling. We have now investigated whether recombinant extracellular GHR can be conjugated to a myristoylated-peptide (mp) tail and inserted into cell membranes to modulate GHR signaling. Recombinant human extracellular domain (1-241) GHR was expressed in Escherichia coli, purified and refolded from cell lysate. The free C-terminal cysteine was then reduced and conjugated to an activated preformed mp tail. The properties of the purified tailed GHR (GHR-mp) were then compared with those of the un-tailed purified GHR1-241. FACS analysis and cell surface binding assays demonstrated that GHR-mp inserted into the cell surface membranes of CHO cells whereas un-tailed GHR1-241 showed no insertion. In a cell based bioassay GHR-mp partially inhibited wild-type GHR signaling whereas GHR1-241 had no effect. Truncated extracellular domain GHR can, when specifically modified with a membrane-localizing mp unit, insert into cell surface membranes and modulate GHR signaling.