The conformational isomerism of the propylene oxide (PO)center dot center dot center dot 2-fluoroethanol (FE) complex has been investigated using molecular beam Fourier-transform microwave spectroscopy complemented with high level ab initio calculations. Rotational transitions of three different binary conformers have been observed experimentally. On the basis of the agreement of the experimental and calculated rotational constants, they could be identified as the three most stable structures, anti G-g+, anti G+g-, and syn G+g-. All the observed structures exhibit a primary O-H center dot center dot center dot O hydrogen bond, an intramolecular O-H center dot center dot center dot F hydrogen bond and two secondary intermolecular C-H center dot center dot center dot F contacts. The two anti conformers, with FE and the PO methyl group on the opposite sides of the oxirane ring, show higher abundances than the syn conformer. In all three observed conformers, FIE remains approximately in its favorable compact gauche conformation. The monofluorination of the molecular lock-and-key model system PO center dot center dot center dot ethanol increases not only the number of possible binary conformers, but also the discrimination energy among them. The superior discrimination ability of FE as compared to ethanol classifies it as a tailored key to the PO lock.