The X-ray structure of muscarone analogues 3 and 4 was determined and compared with that of muscarone (1, iodide and picrate salts), muscarine 2, dioxolane 5, oxathiolane 6, and tetrahydrofuran 7. In order to better define the pharmacological stereoselectivity of muscarone, the conformational profiles of compounds 1, 2, 3, and 5 were analyzed using Allinger's MM2(85) program or, in the case of 4, by 1H NMR spectroscopy. The conformation of the ring in 1 proved similar to that of the other derivatives. MM2 calculations predicted a preferred gauche arrangement of the side chain for 1 and its analogues; such an arrangement was also observed in the solid state of muscarone picrate. Thus, the antiperiplanar arrangement reported for crystalline muscarone iodide appears to be due to crystallographic packing forces. As a consequence, the rationalization of the pharmacological profile of 1 based on the antiperiplanar arrangement is now highly questionable. The lack of stereoselectivity of 4 can be attributed to the absence of a stereocenter at C-2 whereas, in our opinion, there are currently no sound explanations for the low values of eudismic ratios for the muscarone enantiomers.