X-ray diffraction patterns from nerves bathed for about one-half hour in Ringer's solution containing dimethylsulfoxide at concentrations of 10% or more show reflections from a new, highly ordered structure with a repeat period about two-thirds that of native myelin. The proportion of myelin transformed is greater at higher concentrations, and above 40% the native pattern is no longer observed. Replacing the dimethylsulfoxide with Ringer's solution leads to the rapid reappearance of the native diffraction pattern. The effect of dimethylsulfoxide can be accounted for by the loss of water from the spaces between the membrane units without significant modification of the bilayer structure.The molecular interactions that stabilize the spirally wrapped membrane array in the myelin sheath can be characterized by defining conditions that produce reversible structural modifications. Among the reagents we have tested for their effect on myelin structure, dimethylsulfoxide (Me2SO) is distinctive in producing an ordered transformation that is fully reversible.At concentrations above 40%, where the x-ray diffraction patterns show complete transformation of the myelin structure, Me2SO has been shown to produce reversible blockage of nerve conduction in vivo (1) and in isolated nerves (2); at lower concentrations, Me2SO decreases the conduction velocity (3). These physiological effects could be due to the action of Me2SO on both myelin sheath insulation and axon membrane excitability. Whatever the mechanism of these effects, removal of Me2SO restores normal nerve conduction (1-3), and our studies show that the myelin sheath also recovers its normal structure. Native myelins in a variety of nerves have repeat periods in the range 150-185 A (4, 5). The repeating unit is the membrane pair derived by joining cytoplasmic surfaces of the extension from a Schwann or glial cell plasma membrane (6, 7). Electron density profiles show that the membrane bilayers of different myelins have quite similar thickness although the repeat periods may be quite different (8). The spaces between bilayer surfaces comprise about onequarter of the repeat period in rabbit optic nerve and more than one-third the period in rabbit and frog sciatic nerves. Measurement of absolute electron density (9) indicates that these spaces are occupied by a low concentration of protein in water (8). The total water content in the myelin sheath has been estimated to be in the range 30-50% (4,8,10,11 during the appearance of the contracted lattice. This structure formed in Me2SO appears to be a distinct phase derived from native myelin.The exact period of the contracted phase is a function of Me2SO concentration and time of treatment. When first detected, the period is 7-9 A greater than the final value when the contraction has come to equilibrium (Fig. 1). The decrease in period with time roughly parallels the increase in diffracted intensity from the contracted phase. The strong second-order reflection (Fig. 2, top) accounts for about 95% of the total intensit...