The Type 1 parathyroid hormone/parathyroid hormone related peptide receptor is a class B G protein-coupled receptor that demonstrates immunoreactivity in the nucleus as well as cytoplasm of target cells. Our previous studies on the PTH1R have shown that it associates with the importin family of transport regulatory proteins. To investigate the role of the importins in PTH1R nuclear import we used siRNA technology to knock-down the expression of importin in the mouse osteoblast-like cell line, MC3T3-E1. Immunofluorescence microscopy as well as ligand blotting for PTH1R in nuclear fractions of importin siRNA treated cells demonstrated a decrease in nuclear localization of the PTH1R in comparison to control cells. Under normal culture conditions PTH1R is present in both the nucleus and cytoplasm of cells. Serum starvation favors nuclear localization of PTH1R while returning cells to serum or treatment with PTHrP induced its cytoplasmic localization. To address the nuclear export of PTH1R, interactions between PTH1R and CRM1 were investigated. PTH1R and CRM1 coimmunoprecipitated from MC3T3-E1 cells suggesting that CRM1 and PTH1R form a complex in vivo. Following treatment with Leptomycin B, a specific inhibitor of CRM1 mediated nuclear export, PTH1R accumulated in the nucleus. Taken together our studies show that PTH1R shuttles from the nucleus to the cytoplasm under normal physiological conditions and this nuclear-cytoplasmic transport is dependent upon importin / and CRM1.