Intraperitoneal chronic morphine administration to rats produced structural alterations in nerve cells of caudate nucleus, cerebral cortex and hippocampus. All areas studied showed increased alterations related to time elapsed between last morphine injection and fixation of tissue samples. Lesions mainly consisted in vacuolar degeneration of nerve cells. The most extense and intense lesions were observed in hippocampus. Sensorimotor cortex and caudate nucleus showed focal damage. Neurocytotoxic effect of morphine appears to be unrelated to the opiate receptor density in brain areas, and the brain regions susceptible to that effect appears to be different from brain areas related to adaptation to morphine. Effect of morphine on integrity and function of nerve cells mitochondria, interfering with energy production could play an important role in the pathogenesis of neuronal lesions.