The water soluble (WS), urea soluble (US) and urea insoluble (UI) fractions from individual human lenses 1.8 to 65 years of age were isolated from concentric fiber layers. In lenses younger than 19 years, a uniform distribution in the amount of WS, US and UI fractions was found throughout the entire lens. These fractions represent 83, 11.5 and 5.5%, respectively, of the lens dry weight. This composition was observed with the cortical fibers of all lenses examined up to the 65-year old. In the nuclear fiber layers, the proportion of US protein gradually increases in the third to fourth decade of lens growth and appears to have reached a maximum representing 22-24% of the nuclear fiber mass in 50-year and older lenses. A large increase in the amount of the UI fraction to 30% of the fiber mass was observed in lenses between the 5th and 6th decade of lens growth. The change from the cortical to nuclear composition occurs in a narrow region of the lens which becomes more peripheral with aging. The cortical WS fractions were characterized by well defined polyacrylamide gel bands in sodium dodecyl sulfate (SDS). Those of the nuclear fibers were broadened, especially in the 27/29 and 16/18 kilodalton (KD) region. The disappearance of the 20/22 KD bands in the inner cortical and nuclear fibers cannot be accounted for by the small increase in protein insolubilization in these regions of lenses 40 years or younger.