Observing the optical cross-section and electron micrographs of mechanically skinned fibres of frog skeletal muscle, we found that ethylene glycols (EGs) of small (mono-, di-, tri- and tetra-EGs; Mr 62–194) and medium (poly-EGs; Mr 900 and 3350) molecular weights efficiently dehydrate the fibres to shrink them radially without microscopic inhomogeneity. The medium-sized poly-EGs at 30% weight/weight concentration absorbed almost all the evaporable water from the fibre. Passive tension measurement at near slack sarcomere spacing indicated that this dehydration by EGs did not accompany longitudinal fibre shrinkage. Chemically relevant fully hydric alcohols (glycerol, threitol, ribitol and mannitol; Mr 92–182) showed no appreciable dehydrating ability on fibres. An intimate correlation was found between fibre dehydration and CH2-concentration of the solutions. Viscosity measurements indicated that the hydrodynamic radii of the alcohols were comparable to those of the small EGs. Therefore, hydrodynamic radii are not a primary determinant of the dehydrating ability. Additionally, CH2-concentration of EGs but not alcohols was found to correlate intimately with the measured viscosity of the bulk solution of EGs. These results suggested that the interaction between water molecules and CH2-units in crowded cytoplasm of skeletal muscle affects cytoplasm as a whole to realize anisotropic fibre shrinkage.