The increasing intraneuronal accumulation of lipofuscin has been linked to the aging process by a striking linear correlation between the degree of accumulation and chronological age. It has been established that age pigments are soluble in polar and nonpolar solvents; the pigment is autofluorescent and stains with PAS, Sudan black B, Nile blue osmic acid and ferric ferricyanide techniques. Whether all pigments exhibiting these properties are identical, or at least closely related, regardless of the surrounding tissue, animal species and age of the individual, is debatable. Pigment formation has been demonstrated in young and aged animals as well as in individual subjected to experimental stress and to dietetic and environmental interference. Electron microscopic studies in animals have shown a considerable variability in the fine structure of individual lipofuscin granules but the presence of "lucent vacuoles" surrounded by a unit membrane is one of the characteristic features of neuronal lipofuscin in the aged. Recently, electron microscopy, utilizing the freeze-etching technique, has provided convincing evidence which disproves the earlier view that lucent vacuoles are the remnant of lipid material dissolved and removed during the preparation of the tissues for microscopic examination. These vacuoles have also been demonstrated in freshly frozen material not previously fixed or immersed. Vacuolated pigment granules occur earlier in the area postrema than in other regions of the rat brain (Hasan and Heyder 1974). Regional differences in the time sequence of pigment deposition are present.