Age-related changes in both morphological and neurochemical parameters of indol- and catecholaminergic system in the rat brain were examined. A qualitative histochemical survey of the occurrence of aberrant serotonergic fibers in the aged rat brain suggests region-specificity in the process of degeneration. Forebrain areas, such as the caudate-putamen complex, globus pallidus, prefrontal and frontoparietal cortices were consistently affected, whereas serotonergic fibers were only infrequently affected in other areas like septal and amygdaloid nuclei. Neurochemical data similarly revealed regional differences. 5-Hydroxytryptamine levels were increased in the frontoparietal cortex, hippocampus, hypothalamus and the mesencephalic raphe region but remained unchanged in the caudate-putamen complex. 5-Hydroxyindolacetic acid levels were also enhanced in all these areas. Examination of brains of 12-, 18- and 24-month-old rats revealed that aberrant serotonergic fibers were already present at the age of 12 months and their incidence increase with age. There was no difference in the number of serotonergic cells in the dorsal raphe nucleus of young and aged rats. Aberrant tyrosine hydroxylase-immunoreactive fibers were observed only infrequently. Their occurrence showed no overlap with the areas containing aberrant serotonergic fibers. Neurochemical estimates of the levels of catecholamines in young versus aged rat brain areas similarly revealed regional and neurotransmitter specific differences to occur during the process of aging.