The content and distribution of catecholamine-containing formations in the cerebellum of untreated and heroin-treated male rats, was visualized by glyoxylic acid-induced histofluorescence, in an attempt to define the adaptive mechanisms leading to heroin dependent tolerance as well as identify a biological role for these formations. Repeated heroin administration increased the number of specifically organized intracellular catecholamine containing particles, including grain (diameter less than 0.8 microm) and aggregate (diameter greater than 1 microm) forms, in all cerebellar cortical layers examined one hour after the last injection of the drug, relative to controls. The number of grains in all cerebellar cortical layers examined and aggregates in the granular layer, returned to normal or near normal baseline levels within twenty four hours after the last injection of the drug. The analogous baseline of the aggregates in the Purkinje cell layer primarily and the Molecular layer secondarily remained significantly elevated by 86% and 50% respectively, relative to controls. Catecholamine-heroin interactions most likely mediated this elevation that was related directly to the heroin-dependent state of tolerance. These findings indicate that heroin administration to heroin-tolerant rats leads to the formation of unusually large intracellular aggregates with catecholamines in the Purkinje cells of the cerebellum primarily and support a direct role for these formations in the modulation of biogenic amine bioavailability. We conclude that adaptation to drug exposure involves multiple homeostatic interactions, with sympathetic activation at the level of catecholamine reorganization and redistribution playing a major role in rat cerebellar cortex.