Follicle-stimulating hormone (FSH) receptor (FSHR), a member of the G protein-coupled receptor (GPCR) superfamily, is present in the plasma membrane of ovarian granulosa cells and testicular Sertoli cells. FSH regulates normal ovarian follicle development and spermatogenesis through FSHR. The extracellular domain of FSHR (FSHR_ECD) is a weakly associated homodimer in the recently solved crystal structure of FSH in complex with FSHR_ECD. However, there is currently no biochemical data that demonstrates that FSHR exists as a dimer or higher order oligomer in cell membranes. A fluorescence resonance energy transfer (FRET) assay was used to determine whether full-length native FSHR is an oligomer. FSHR-specific monoclonal antibody (mAb) or Fab fragments, labeled with two different fluorophores, allowed the study of non-tagged receptor in situ. Unoccupied FSHR exhibited strong FRET profiles in situ. Complementary co-immunoprecipitation experiments of myc- or FLAG-tagged FSHR indicated that FSHR forms oligomers early in receptor biosynthesis. No effect of FSH treatment was observed. Thus, immature forms of FSHR, not yet fully processed, were observed to co-immunoprecipitate. An unexpected observation was made that the C-terminal epitope tags are removed from FSHR prior to arrival at the cell surface. These results provide the first evidence for oligomers of full length FSHR in situ and for C-terminal proteolytic processing of FSHR, and that both events take place during biosynthesis. This may explain how heterozygous mutations in the FSHR gene which affect receptor trafficking may be ameliorated by oligomer formation.