To examine water diffusion in the crystalline lens and sugar cataracts in the rabbits in vivo. Water self-diffusion in the lens cortices of alloxan-diabetic and galactosemic rabbits was examined with magnetic resonance imaging (MRI). The animals were positioned in a 4.7-tesla animal system in conjunction with a 1-inch surface coil for the eye. Diffusion-weighted MRI was conducted using a pulsed-gradient spin-echo sequence with a gradient strength of 0-6 Gs/cm in the primary and secondary coordinates. Other MRI parameters included TR (repetition time)/TE (echo time) = 2,000/10 ms, a field of view of 4 cm, and a 256 x 128 matrix. There appeared an increase in water relaxation resulting in an increase of % (equatorial cortex depth)/(lens long axis) from 18 in the lenses of normal rabbits to 30.4 and 39.9 in the lenses of galactosemic and diabetic rabbits, respectively. In addition, water diffusion changed in the lens of the diabetic rabbit with an increasing intracellular fluidity along the long axis of the cortical fibers, for example, the diffusion coefficient changed from a normal of 0.48 to 0.96 x 10(-5) cm2 s-1 in the lens of the diabetic rabbit. These results showed altered water mobility due to subcellular disturbances occurring before any apparent lens opacities. Further, there also was an increase in the water diffusivity in the aqueous humor from a normal of 1.77 to 2.67 x 10(-5) cm2 s-1 in the galactosemic rabbit eye suggesting an increase in either free water proportion or thermal convection. Resistance to water self-diffusion appeared to relate to lens fiber orientation and intracellular protein order. Diffusion imaging therefore can be used to examine water self-diffusion to detect early osmotic alteration of lens fibers.