A number of epimeric pairs of 3-X-trans-2,4-dioxa-3-Y-3-phosphabicyclo[4.3.0]nonanes (1, X = OCH3, Y = 0; 2, X = OCH3, Y = S; 3, X = OPh, Y = O; 4, X = OPh, Y = S; 5, X = Cl, Y = 0; 6, X = CI, Y= S; 7, X = N(CH3)2, Y = 0; 8, X = N(CH3)2, Y = S; 9, X = S, Y = 0; 10, X = 0, Y = 0) have been prepared and their configuration and conformation studied by 31p and 1H NMR. The cis isomers 1a-6a and the trans isomers 7b and 8b are shown to populate exclusively chair conformation 18. Their diastereomers 1b-6b, 7a, and 8a, however, exist as an equilibrium between chair conformation 18 and twist conformation 19. The mole fraction of twist is found to vary with the nature of the exocyclic substituents on the phosphorus atom, being maximal for the chloro compounds 5b and 6b. In addition, it is shown that the chair twist equilibrium is solvent-sensitive. The charged compounds 9a, 9b, and 10 are in a chair conformation. The position of the negatively charged sulfur atom has no influence on the preferred conformation of the phosphorothioates 9a and 9b. The results for 9a and 9b are discussed in relation to the difference in biological activity of (Sp)- and (Rp)-cAMPS.