Single viable fiber cells have been isolated from the cortex of rat ocular lens by proteolytic digestion of the intact lens in calcium-free media. In isomolar sucrose, the isolated cells maintain their fiber-shaped morphology and exclude trypan blue. The surface morphology of the isolated fiber cells appears to be largely unaffected by the isolation procedure. The concentrations of adenine nucleotides, GSH, GSSG and the rate of glycolysis in the isolated fiber cells were comparable to those in the cortex. Upon perfusion of the tissue chamber with Ringer's solution, the fiber cells undergo a series of transformations, beginning with cell swelling, periodic blebbing along the longitudinal cellular axis, and eventual disintegration of the fiber into a number of resealed globules or round cells which resemble light-scattering areas in human cortical and supranuclear cataract. This disintegrative globulization of the fiber cells appears to be mediated by calcium influx, as it was prevented or delayed by a reduction in extracellular calcium concentration, verapamil or lanthanum. Since disturbances in calcium homeostasis are associated with various forms of cataract, such Ca(2+)-mediated disintegrative globulization of the fiber cells may be responsible for the formation of light scattering centers during cataractogenesis.