Two constructs of transgenic mice, TG61 and TG72, containing HIV-1 protease linked to lens alpha A-crystallin promoter develop cataract. The TG61 construct exhibits cataractogenesis in utero, while in the TG72 construct frank opacities appear 24 days (homozygotes) and 26 days (hemizygotes) after birth. Differential scanning calorimetry and thermogravimetric analysis studies indicate that the hydration of lenses is strongly correlated with cataractogenesis. In all clear lenses (normal and precataractous) the total water content was the same, 68%, and increased upon opacification. The bound water, measured as percentage nonfreezable water of the total water, decreased upon cataract formation, indicating a syneretic process. On the other hand, the bound water expressed as grams of nonfreezable water per gram dry weight increases upon opacification. This implies that proteolysis and subsequent enhanced hydration is the primary supramolecular event in cataractogenesis and that syneresis in the lens of transgenic mice is of secondary importance.