The conformational state of cyclosporine in liquid crystalline spray-dried powders and the solution structure of cyclosporine, in a series of organic solvents where solvent dipole and hydrogen bonding ability varied, were determined. Fourier transformed infrared spectra (FTIR) were obtained on cyclosporine powders, and cyclosporine solutions in a series of organic solvents. Tetragonal crystalline cyclosporine revealed an intermolecular aggregate band at 1614 cm Γ1 , a b-sheet band at 1627 cm Γ1 , a g-loop band at 1648 cm Γ1 , a g-turn band at 1658 cm Γ1 (formed from a hydrogen bond between D-Ala 8 NH and MeLeu 6 C --O) and a Type II b-turn band at 1673 cm Γ1 (centered at the hydrogen bond betweenVal 5 NH to Abu 2 C --O). A similar conformation was observed in chloroform or octanol (apolar), where a second b-sheet band emerged at 1638 cm Γ1 and a turn structure associated with the b-OH on MeBmt 1 appeared at 1685 cm Γ1 . However, the spray dried liquid crystal structure resembled the solution conformation in acetone or acetonitrile (hydrogen bond acceptor). The conformation in acetone suggested that the bsheet, g-loop, Type II b-turn and MeBmt 1 turn remained intact. Interestingly, the spraydried powder conformations did not resemble the solution structure of the solvent (ethanol) from which they had been obtained. The conformation in ethanol and methanol (hydrogen bond donor) showed only b-sheet, g-turn, MeBmt 1 turn structure. Only a small population of molecules retained the Type II b-turn. Finally, cyclosporine is essentially insoluble in water, so the water conformation has never been elucidated; however, a conformation resembling the active structure was obtained in a cosolvent solution containing both hydrogen bond donors and acceptors. This conformation is in good agreement with molecular modelling studies where cyclosporine is docked in the active site of cyclophilin. Spray-dried cyclosporine formed a liquid crystal that can be described as maintaining the Type II b-turn, b-sheet, and g-loop structures seen in crystalline material. However, the hydrogen bond between D-Ala 8 NH and MeLeu 6 C --O was disrupted.