Fibroblast growth factor (FGF) is a potent inducer of fiber differentiation in lens epithelial explants from neonatal rats as assessed by the accumulation of fiber-specific proteins (beta- and gamma-crystallins) and the progression of cells through a sequence of morphologic events characteristic of fiber differentiation in situ. Because new fibers normally are formed in the lens throughout life, the authors questioned whether epithelial cells from rats of all ages are induced to differentiate into fibers by FGF. Earlier studies have shown that, with the increasing age of the donor rat, the lens epithelial explants had a reduced ability to accumulate beta- and gamma-crystallins in response to FGF. To determine if the characteristic morphologic events in fiber differentiation were induced by FGF in explants from rats of different ages, an ultrastructural study was done. Using the time of appearance and level of expression of the following morphologic markers of fiber differentiation: (1) cell elongation, (2) reduction of cytoplasmic organelles, (3) formation of cell processes, and (4) fiber denucleation, the level of fiber differentiation induced by FGF was assessed in explants from 10-, 21-, 100-, and 175-day-old rats. These results showed that, with increasing donor age, epithelial cells showed a gradual decline in responsiveness to FGF. This was manifested by a slower progression through the sequence of fiber-specific structural events as the age of the donor rat increased. At all ages studied, cells in the central region of explants responded more slowly than cells from the peripheral region. The finding that FGF induces events in fiber differentiation, albeit at a slower rate, in explants from mature rats supports the hypothesis that FGF in the eye continues to play a role in inducing lens epithelial cells at the lens equator to differentiate into fibers throughout life.