Natural quartz single crystals were experimentally deformed in two orientations: (1) ⊥ to one prism plane and (2) in O + orientation at 900 and 1000°C, 1.0 and 1.5 GPa, and strain rates of ~1 × 10 À6 s À1. In addition, hydrostatic and annealing experiments were performed. The starting material was milky quartz, which consisted of dry quartz with a large number of fluid inclusions of variable size up to several 100 μm. During pressurization fluid inclusions decrepitated producing much smaller fluid inclusions. Deformation on the sample scale is anisotropic due to dislocation glide on selected slip systems and inhomogeneous due to an inhomogeneous distribution of fluid inclusions. Dislocation glide is accompanied by minor dynamic recovery. Strongly deformed regions show a pointed broad absorption band in the ~3400 cm À1 region consisting of a superposition of bands of molecular H 2 O and three discrete absorption bands (at 3367, 3400, and 3434 cm À1). In addition, there is a discrete absorption band at 3585 cm À1 , which only occurs in deformed regions and reduces or disappears after annealing, so that this band appears to be associated with dislocations. H 2 O weakening in inclusion-bearing natural quartz crystals is assigned to the H 2 O-assisted dislocation generation and multiplication. Processes in these crystals represent recycling of H 2 O between fluid inclusions, cracking and crack healing, incorporation of structurally bound H in dislocations, release of H 2 O from dislocations during recovery, and dislocation generation at very small fluid inclusions. The H 2 O weakening by this process is of disequilibrium nature because it depends on the amount of H 2 O available.